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Objective: Breast cancer and breast cancer-directed radiation therapy (RT) may increase the risk of late effects, such as hypothyroidism. We conducted a systematic review and meta-analysis to investigate the association between breast cancer, RT, and risk of hypothyroidism in breast cancer survivors. Methods: Through February 2022, we searched PubMed, EMBASE, and references of relevant articles, to identify papers on breast cancer and breast cancer-directed RT and subsequent risk of hypothyroidism. Articles were screened by title and abstract and reviewed for eligibility. We used a pre-formed data extraction sheet and identified key design elements that could potentially introduce bias. The main outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in breast cancer survivors versus women without breast cancer, and in breast cancer survivors according to the receipt of RT to the supraclavicular lymph nodes. We used a random-effects model to calculate pooled RRs and associated 95% confidence intervals (95% CI). Results: From 951 papers screened by title and abstract, 34 full-text papers were reviewed for eligibility. We included 20 studies published between 1985 and 2021–19 were cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk associated with RT to the supraclavicular region (RR = 1.69, 95% CI: 1.16, 2.46). The most important limitations of the studies were small sample size yielding estimates with low precision, and lack of data on potential confounders. Conclusion: Breast cancer and radiation therapy to the supraclavicular lymph nodes is associated with an increased risk of hypothyroidism.

Sexual interest in children is an important factor contributing to sexual (re)offending against children. The current state of research makes it difficult to conclude if people with pedophilia are overly interested in children, or have lower interest in adults, or both. This is relevant knowledge in treatment for preventing sexual (re)offenses against children. This study aimed to systematically analyze sexual interest in both children and adults in samples of men with pedophilia and comparison groups. A total of 55 studies (N = 8465) were included in four meta-analyses and a systematic review. Most included studies considered people who had sexually offended against children (PSOC; nPSOC = 5213). Results indicated that PSOC with pedophilia did not have a clear sexual preference for either children or adults. Compared to comparison groups, they had more absolute sexual interest in children and lower sexual interest in adults. We conclude that the lack of sexual interest in adults may be a relevant factor in PSOC with pedophilia. More studies are needed to disentangle sexual interest in children from sexual interest in adults, while using carefully matched comparison groups and appropriate research designs.

Sexual interest in children is an important factor contributing to sexual (re)offending against children. The current state of research makes it difficult to conclude if people with pedophilia are overly interested in children, or have lower interest in adults, or both. This is relevant knowledge in treatment for preventing sexual (re)of-fenses against children. This study aimed to systematically analyze sexual interest in both children and adults in samples of men with pedophilia and comparison groups. A total of 55 studies (N = 8465) were included in four meta-analyses and a systematic review. Most included studies considered people who had sexually offended against children (PSOC; nPSOC = 5213). Results indicated that PSOC with pedophilia did not have a clear sexual preference for either children or adults. Compared to comparison groups, they had more absolute sexual interest in children and lower sexual interest in adults. We conclude that the lack of sexual interest in adults may be a relevant factor in PSOC with pedophilia. More studies are needed to disentangle sexual interest in children from sexual interest in adults, while using carefully matched comparison groups and appropriate research designs.

Background This paper is a systematic review and meta-analysis of the efficacy of available medications for the treatment of restricted/repetitive behavior (RRBs) in Autism Spectrum Disorder (ASD). Method We searched MEDLINE, Embase, PsycINFO, The Cochrane Library (Cochrane Database of Systematic Reviews (CDRS), the Cochrane Central Register of Controlled Trials (CENTRAL), database of Abstracts of Reviews of Effects (DARE)), Scopus, Epistimonikos, Clinicaltrials.gov, and included all randomized controlled trials published after 1993 that were directed at RRBs in patients with ASD of all ages. We extracted the relevant data from the published studies with a predefined data extraction form and assessed the risk of bias. The primary outcomes were change in restricted/repetitive behavior. We performed a meta-analysis using the random effect model and included studies with given mean and standard deviation. This study is registered with PROSPERO number CRD42018092660). Results We identified 14 randomized controlled trials that met initial inclusion criteria. After closer inspection, nine trials – involving 552 patients in total – were included in the final analysis. The meta-analysis found no significant difference between medications (including fluvoxamine, risperidone, fluoxetine, citalopram, oxytocin, N-Acetylcysteine, buspirone) and placebo in the treatment of RRBs in ASD (P = 0.20). Similarly, the sub-group meta-analysis also showed no significant difference between Selective Serotonin Reuptake Inhibitor (SSRIs) and placebo in the treatment of RRBs in ASD (P = 0.68). There was no evidence of publication bias. Conclusion This meta-analysis finds little support for the routine use of medications to treat restricted/repetitive behaviors in Autism Spectrum Disorder. Further research of large, balanced trials with precise assessment tools and long-term follow-up are needed. Trial registration The study protocol is registered in PROSPERO (Reference number: CRD42018092660).

Objective: To characterize and explain variation in the comparative effectiveness of self-care interventions on relevant outcomes of chronic illness compared with controls. Design: Meta-analysis and meta-regression. Methods: Data extraction was framed within the context of a previously-published scoping review of randomized trials designed to enhance self-care in type 2 diabetes mellitus, heart failure, hypertension, asthma, coronary artery disease, and chronic obstructive pulmonary disease (published between 2008 and 2019). Data were pooled using random-effects meta-analyses. Meta-regression was used to test the effect of potential moderators on trial effectiveness. Results: 145 trials involving 36,853 participants were included. Overall, the effect size of self-care interventions on improving outcomes was small (Hedges g = 0.29 (95% CI = 0.25-0.33), p < 0.001) with statistically significant heterogeneity across trials (Q = 514.85, p < 0.001, I2 = 72.0%). A majority of trials (n = 83, 57.2%) were rated as having a high risk of bias. There was no statistically significant difference in trial effectiveness based on the use of theory, specific components of self-care addressed, the number of modes of delivery, the number of behavioral change techniques, specific modes of delivery, specific behavioral change techniques, intervention duration, total number of hours of intervention, or either participant age or gender.Conclusions: Self-care interventions are modestly effective in improving outcomes. Poor trial quality limits the strength of conclusions in this area of science. There is much to be done to enhance the design, conduct and reporting of self-care trials in order to gain more insight into the effectiveness of self-care interventions.

Background: Chronic pain has a large individual and societal burden. Previous reviews have shown that internetbased cognitive-behavioral therapy (iCBT) can support patients' pain coping. However, factors related to participant experience of iCBT and effective and safe iCBT delivery for chronic pain have not recently been summarized. Objective: The aim of this review was to give an overview of the efficacy of guided iCBT for chronic pain on psychological, physical, and impact on daily life outcomes, including factors that inform optimal delivery. Methods: Cochrane, Emcare, Web of Science, PubMed, PsycINFO, and Embase were systematically searched from inception to 11 February 2022. Randomized controlled trials on guided iCBTs for adults with chronic pain were included with a broad range of outcomes. Results: The search yielded 7406 studies of which 33 studies were included totaling 5133 participants. ICBT was more effective than passive control conditions for psychological (ES = 0.34-0.47), physical (ES = 0.26-0.29), and impact outcomes (ES = 0.38-0.41). ICBT was more effective than active control conditions for distress (ES = 0.40), pain acceptance (ES = 0.15), and pain interference after outlier removal (ES = 0.30). Longer treatments were associated with larger effects for anxiety and quality of life than shorter treatments. Mode of therapist contact (synchronous, asynchronous or a mix of both) was not related to differences in effect sizes in most outcomes. However, studies with mixed and synchronous contact modes had higher effects on pain self-efficacy than studies with asynchronous contact modes. Treatment satisfaction was high and adverse events were minor. Dropout was related to time, health, technical issues, and lack of computer skills. Conclusions: Guided iCBT is an effective and potentially safe treatment for chronic pain. Future research should more consistently report on iCBT safety and detail the effectiveness of individual treatment components to optimize iCBT in clinical practice.

Background Previous studies evaluated the association of IL-4 C33T polymorphism and risk of bronchial asthma but failed to establish a consistent conclusive association. In the present meta-analysis, we intend to define a more reliable estimate of the association in the presence of filling published literature. Methods An exhaustive search in Web of Science, Scopus, and PubMed databases was performed to identify all relevant publications before September 2020, and 24 publications (28 studies) with 6587 cases and 8408 controls were included in final analysis. The association between polymorphism and risk of asthma were measured by Odd ratios (ORs) and 95% confidence intervals (CIs). Moreover, Cochran’s Q and the I2 statistics were used to evaluate the degree of heterogeneity between studies. Results In the overall study populations, a significant positive association was detected under all genotype models and announced the IL-4 C33T polymorphism as a potential risk factor in the pathogenesis of asthma. In the subgroup analysis by age, a significant association between IL-4 C33T polymorphism and risk of asthma in different age groups was identified in allelic model, which highlighted the predisposing role of the T allele for the asthma risk in all three age groups. Furthermore, the results of subgroup analysis by continent were heterogenous. Accordingly, IL-4 C33T polymorphism was a risk factor in Europeans (all models except heterozygote comparison), Americans (all models except recessive and homozygote comparison) and Asians (just recessive and allelic model). Finally, the ethnicity-specific analysis disclosed a significant association between IL-4 C33T polymorphism and asthma risk in Caucasians (all genotype models except heterozygote comparison), while this association was not significant in African-Americans. Conclusions This study suggests that IL-4 C33T polymorphism potentially acts as a risk factor for asthma in different ethnicities and age groups.

Background and Aim: Primary experience of intrauterine period is the essential basis of the life for the embryo. Therefore paying attention to it can lead to reduced health inequities. The aim of this study was to investigate the relationship of the structural and intermediate social determinants of health with low birth weight in Iran Materials and Methods: This systematic review and meta-analysis was performed based on the studies conducted in Iran. We searched seven databases (Iranmedex, Magiran, SID, Irandoc, PubMed, Google Scholar and Scopus) by using keywords of social determinants of health, low birth weight and equivalents of them to find relevant articles published between 2000 and 2016. Data from relevant studies were extracted by two persons separately and evaluated by using the Stroop checklist. After extracting the required data, they were combined using a random model and the heterogeneity of the studies was evaluated by the I2 index. STATA-11 software was used for data analysis. Result: Thirty articles were analyzed in this systematic review and meta-analysis. The sample size included 42142 people. The overall odds ratios for the relationship of the structural and intermediate social determinants of health with LBW were estimated as 1.52 (1.24%-1.85: %95 CI) and 2.24 (1.85%-2.71: %95 CI) respectively. Conclusion: Considering the importance of low birth weight in the health of newborns, basic measures should be taken to prevent the occurrence of this problem by identification of its risk factors and people at risk, improvement of living standards and regular prenatal care, counseling before pregnancy and improvement of the nutritional status of pregnant women. Keywords: Low birth weight, Pregnancy outcome, Social determinants of health, Meta –analysis. Received: May 13, 2017 Accepted: Apr 9, 2018

Background and objective Lung cancer is one of the most common cancers worldwide, especially in China. It has been proved that matrix metalloproteases (MMPs) play a key role in malignant cell metastasis. There have been a considerable number of studies investigating MMP polymorphisms in relation to various cancers. However, the associations of MMP polymorphisms with risk of lung cancer are lack of consistency. The aim of this study is to assessthe association of MMP polymorphisms with risk of lung cancer by conducting a Meta -analysis from all eligible casecontrol studies published to date. Methods To identify all studies that examined the association of polymorphisms in the promoter of MMP1, MMP2 and MMP9 with lung cancer, we conducted a computerized literature search of PubMed and MEDLINE database (before March, 2009). Two investigators independently extracted the data and reached a consensus on all items. Results Eight case-control studies, including 4 467 lung cancer cases and 4 051 controls, were selected for Meta -analysis to better assess the purported associations of common MMPs polymorphisms with risk of lung cancer. Our results suggest that MMP2 -735C/T polymorphism is significantly modified risk of lung cancer. Comparing with the wild-735C allele, the variant T allele decreased risk of developing lung cancer (OR=0.72, 95%CI: 0.61-0.85, P =0.0001). Other polymorphisms, including MMP1 -1607 1G/2G, MMP2 -1306C/T and MMP9 -1562C/T, are not associated with risk of lung cancer. Conclusion The present study indicates that the MMP2 -735C/T polymorphism is associated with the risk of lung cancer. Lager studies should be required to warrant the association of MMP9-1562C/T polymorphism with risk of lung cancer.

Background and objective In the past years, many reports on Kanglaite were publicated in China, researchers across the country. The aim of this study is to review the effectiveness and safety of Kanglaite for treating advanced non-small-cell lung cancer. Methods Authors searched the Cochrane Library, Pubmed, Embase, Cancerlit,CBM, CNKI and VIP. Mannual and additional search were also conducted. All randomized controlled trials/quasi- RCT comparing Kanglaite with other lung cancer treatment were included. Two reviewers independently performed data extraction and appraised the publications using the Juni instrument, disagreements were resolved by consensus. Double data were entered and analyzed by RevMan 4.2 software are by Cochrane Collaboration. Results Sixteen reports wereincluded in the meta-analysis. The quality of 16 studies was low. Pooling data of 5 studies indicated that the effect of Kanglaite+NP (Vinorelbine+Cisplatin) was better than NP with RR 1.46, 95% Confidence Interval 1.13 to 1.91. Pooling data of 3 studies of MVP (Mitomycin+Vindsine+ Cisplatin) plus Kanglaite indicated that the effect was better with RR 1.84, 95%CI 1.22 to 2.76. Pooling data of 2 studies showed that the effect of GP (Gemcitabine+Cisplatin) plus Kanglaite was better than GP with RR 1.63, 95%CI 1.09 to 2.43. Fourteen studies revealed that Kanglaite may reduce the side-effectinduced by regular treatment. Ten studies showed regular treatment plus Kanglaite can stabilite/improve quality of life. Conclusion Kanglaite can enhance clinical effect of regular treatment, reduce side-effect and stabilite/improve quality of life, but the effect of Kanglaite being used in clinical settings needs to be confirmed by further large and multicenter.