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Effects of mild/asymptomatic COVID-19 on semen parameters and sex-related hormone levels in men: a systematic review and meta-analysis.
Che, BW, Chen, P, Yu, Y, Li, W, Huang, T, Zhang, WJ, Xu, SH, He, J, Liu, M, Tang, KF
Asian journal of andrology. 2023;25(3):382-388
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Various studies have shown that coronavirus disease 2019 (COVID-19) can cause more harm and a higher mortality rate to men. However, the literature does not clearly show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause serious and lasting damage to male reproductive function. The aims of this study were to explore the effects of mild/asymptomatic COVID-19 on semen parameters and sex-related hormone levels and to analyse the relationship between semen parameter values and semen collection time after infection, fever, and severity of COVID-19. This study is a systematic review and meta-analysis of thirteen studies of which only five were included in the meta-analysis. Results show that COVID-19 has a certain effect on male reproductive function in the short term especially within about 70 days after infection. Additionally, fever after infection only had a significant effect on sperm concentration. Authors conclude by recommending the avoidance of pregnancy for a short period of time when the male partner has been infected with COVID-19.
Abstract
Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I2 = 0; P = 0.003), total sperm count (I2 = 46.3%; P = 0.043), progressive motility (I2 = 50.0%; P < 0.001), total sperm motility (I2 = 76.1%; P = 0.047), and normal sperm morphology (I2 = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.
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Diabetes mellitus, prediabetes and the risk of Parkinson's disease: a systematic review and meta-analysis of 15 cohort studies with 29.9 million participants and 86,345 cases.
Aune, D, Schlesinger, S, Mahamat-Saleh, Y, Zheng, B, Udeh-Momoh, CT, Middleton, LT
European journal of epidemiology. 2023;38(6):591-604
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Diabetes mellitus and prediabetes may increase an individual’s risk for Parkinson’s disease (PD), however the research completed to date has been controversial. This meta-analysis of 15 observational studies with 86,345 individuals with PD aimed to update the research on PD risk for individuals with diabetes or prediabetes and determine possible reasons for the ambiguity of previous research. The results showed that compared to people without diabetes, those with, were at a 27% increased relative risk of PD and a 4% increase amongst those with prediabetes. Individuals with a history of complications alongside diabetes were at a higher risk than those without. It was concluded that the risk of developing PD is increased amongst individuals with diabetes. This study could be used by healthcare professionals to understand that individuals with diabetes may be at an increased risk for PD and should be monitored. However, as this is based on observational studies, there is a chance that PD increases the risk for diabetes and not the reverse.
Abstract
A diagnosis of diabetes mellitus and prediabetes has been associated with increased risk of Parkinson's disease (PD) in several studies, but results have not been entirely consistent. We conducted a systematic review and meta-analysis of cohort studies on diabetes mellitus, prediabetes and the risk of PD to provide an up-to-date assessment of the evidence. PubMed and Embase databases were searched for relevant studies up to 6th of February 2022. Cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes, prediabetes and Parkinson's disease were included. Summary RRs (95% CIs) were calculated using a random effects model. Fifteen cohort studies (29.9 million participants, 86,345 cases) were included in the meta-analysis. The summary RR (95% CI) of PD for persons with diabetes compared to persons without diabetes was 1.27 (1.20-1.35, I2 = 82%). There was no indication of publication bias, based on Egger's test (p = 0.41), Begg's test (p = 0.99), and inspection of the funnel plot. The association was consistent across geographic regions, by sex, and across several other subgroup and sensitivity analyses. There was some suggestion of a stronger association for diabetes patients reporting diabetes complications than for diabetes patients without complications (RR = 1.54, 1.32-1.80 [n = 3] vs. 1.26, 1.16-1.38 [n = 3]), vs. those without diabetes (pheterogeneity=0.18). The summary RR for prediabetes was 1.04 (95% CI: 1.02-1.07, I2 = 0%, n = 2). Our results suggest that patients with diabetes have a 27% increased relative risk of developing PD compared to persons without diabetes, and persons with prediabetes have a 4% increase in RR compared to persons with normal blood glucose. Further studies are warranted to clarify the specific role age of onset or duration of diabetes, diabetic complications, glycaemic level and its long-term variability and management may play in relation to PD risk.
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Systematic review and meta-analysis of candidate gene association studies of benign prostate hyperplasia.
Lin, L, Li, P, Liu, X, Xie, X, Liu, L, Singh, AK, Singh, HN
Systematic reviews. 2022;11(1):60
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Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate which can cause urinary dysfunction and may affect the quality of life of patients. Polymorphism in several genes has been linked to the high susceptibility of BPH. The aim of this study was to analyse genetic variations in important genes towards the susceptibility of BPH. This study is a systematic review and meta-analysis of twenty-three case-control studies (11 for CYP17 [gene], 10 for VDR - vitamin D receptor [a member of the steroid/ thyroid hormone receptor family] and 4 for ACE - angiotensin-converting enzyme [component of the renin–angiotensin system] polymorphisms). The sample size in each study ranged from 20 to 588 participants. Results show that genetic polymorphism in the ACE gene was significantly associated with the risk of BPH when compared with control subjects. Whereas there was a negative association for the polymorphism located in VDR and CYP17 genes with the risk of BPH. Authors conclude that larger studies with prospective data and larger sample sizes are required.
Abstract
BACKGROUND Benign prostate hyperplasia (BPH) is the most common urological problem in elderly males. Recent studies have reported polymorphism in various metabolic genes in BPH. However, their association with the susceptibility of BPH is still inconsistent. Here, we systematically reviewed and performed a meta-analysis of CYP17, VDR, and ACE genes to determine their precise association with the risk of BPH. METHODS A comprehensive literature search for published studies on candidate gene associations involving vitamin D receptor (VDR), angiotensin-converting enzyme (ACE), and CYP17 genes with the risk of BPH was done up to April 2020 in PubMed, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar databases. Fixed/random effects models were used to estimate the odd's ratio (OR) and 95% confidence intervals (CIs). Begg's funnel plot was used to assess the potential for publication bias. RESULTS We found a total of 23 studies containing 3461 cases and 3833 controls for these gene polymorphisms. A significant association of ACE gene polymorphism was observed under the recessive (II vs. ID + DD) model for BPH susceptibility compared to control subjects (overall OR = 1.67, 95% CI = 1.03-2.73). Similar trends were observed for ACE gene polymorphism in Caucasian (OR = 6.18, 95% CI = 1.38-27.68) and Asian (OR = 1.42, 95% CI = 0.99-2.03) populations under study. No significant association was observed in VDR and CYP17 gene polymorphisms in any dominant or recessive models. CONCLUSION Significant OR demonstrated the implication of ACE gene polymorphism in the proliferation of prostate tissue, which in turn is associated with BPH susceptibility. However, prospective studies at large scale and sample size are needed to confirm the current findings.
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Association Between Prediabetes and Erectile Dysfunction: A Meta-Analysis.
Jin, M, Yuan, S, Wang, B, Yi, L, Wang, C
Frontiers in endocrinology. 2021;12:733434
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Erectile dysfunction (ED) is a common sexual dysfunction in men, which is defined as the failure to achieve or maintain an erection for satisfactory sexual intercourse. Besides aging, diabetes mellitus has also been recognised as a major risk factor for ED. The aim of this study was to systematically evaluate the association between prediabetes and ED. This study is a meta-analysis of nine observational studies, including five matched case-control studies and four cross-sectional studies. Results show that compared to men with normoglycemia, those with prediabetes were associated with higher prevalence of ED. Further subgroup analysis showed that mean age of the male participants in each study may affect the results as the association between prediabetes and ED seemed to be stronger in studies with younger men (mean age <50 years) than that in studies with older men (mean age ≥50 years). Authors conclude that prediabetes is associated with higher prevalence of ED, which may be independent of age of the males and may be stronger in young men.
Abstract
BACKGROUND Diabetes has been associated with the increased risk of erectile dysfunction (ED). However, previous studies evaluating the association between prediabetes and ED showed inconsistent results. We performed a meta-analysis of observational studies to systematically evaluate the above association. METHODS Relevant observational studies were retrieved by search of PubMed, Embase, and Web of Science databases. A random-effect model which incorporated the potential intra-study heterogeneity was used for the meta-analysis. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcome. RESULTS Nine studies (five matched case-control studies and four cross-sectional studies) were included. Age were adjusted or matched in all of the studies. Pooled results showed that compared to men with normoglycemia, men with prediabetes were associated with higher prevalence of ED (odds ratio = 1.62, 95% confidence interval: 1.28 to 2.07, P < 0.001; I2 = 78%). Subgroup analyses showed that the association was not significantly affected by definition of prediabetes, diagnostic tool for ED, or controlling of additional variables besides age (both P for subgroup difference > 0.05). However, the association between prediabetes and ED seemed to be stronger in case-control studies than that in cross-sectional studies, and in studies with younger men (mean age < 50 years) than in those with older men (mean age ≥ 50 years; both P for subgroup difference < 0.05). CONCLUSIONS Prediabetes is associated with higher prevalence of ED, which may be independent of age of the males and may be stronger in young men.
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The effect of exercise on anxiety in the elderly worldwide: a systematic review and meta-analysis.
Kazeminia, M, Salari, N, Vaisi-Raygani, A, Jalali, R, Abdi, A, Mohammadi, M, Daneshkhah, A, Hosseinian-Far, M, Shohaimi, S
Health and quality of life outcomes. 2020;18(1):363
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Anxiety occurs in all age groups. In the US 15-52% of the elderly have anxiety related symptoms and these tend to manifest as physical problems such as insomnia, behavioural, sensory, urinary, cardiovascular, and gastrointestinal disorders. The elderly are more prone to anxiety due to loss or reduction of self-esteem, reduction of activity and stimulation, loss of friends and relatives, loss of physical independence, chronic diseases, changes in daily life or living environment, fear of death and lack of social support. Physical activity is a simple, cheap therapeutic approach. There are several preliminary studies on the effect of exercise training on reducing anxiety in the elderly, but there are inconsistencies between their results. The purpose of this meta-analysis is to resolve such inconsistencies. This meta-analysis included 19 studies published from 1999 until December 2019. Results of this study showed that sport significantly reduces anxiety in the elderly. Therefore, a regular exercise plan can be considered as a part of the elderly care program.
Abstract
BACKGROUND Physical activity and exercise are among the most important, simplest, and cheapest approaches to anxiety treatment, especially for the elderly. Their positive effects on improvement of mental disorders in the elderly have attracted a considerable level of attention. Therefore, the present study was conducted to determine the effect of sport on reducing anxiety in the elderly using meta-analysis. METHODS In this study, national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed, and Web of Science were searched to find studies published electronically from 1999 to 2019. Heterogeneity between the collected studies was determined using the Cochran's test (Q) and I2. Due to presence of heterogeneity, the random effects model was used to estimate the standardized mean difference of sport test scores obtained from the measurement of anxiety reduction among the elderly, between the intervention group before and after the test. RESULTS In this meta-analysis and systematic review, 19 papers finally met the inclusion criteria. The overall sample size of all collected studies for the meta-analysis was 841 s. Mean anxiety score before and after intervention were 38.7 ± 5.6 33.7 ± 3.4 respectively, denoting a decrease in anxiety score after intervention. CONCLUSION Results of this study indicates that Sport significantly reduces Anxiety in the Elderly. Therefore, a regular exercise program can be considered as a part of the elderly care program.
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Effect of Ramadan Fasting on Weight and Body Composition in Healthy Non-Athlete Adults: A Systematic Review and Meta-Analysis.
Fernando, HA, Zibellini, J, Harris, RA, Seimon, RV, Sainsbury, A
Nutrients. 2019;11(2)
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Ramadan is the Islamic tradition of fasting for one month from sunrise to sunset. Generally, Ramadan is known to impact weight. This systematic review and meta-analysis specifically evaluated the effects of Ramadan on both weight and body mass (fat mass and fat-free mass), pre and post fasting, and in the context of there being no attempt to influence physical activity or diet. The meta-analysis was conducted on 70 publications, 90 comparison groups and 2947 participants. Data was also extracted for diverse sub-groups such as overweight/obese, gender and geographical location. The results showed that Ramadan promoted a significant reduction in weight pre and post fasting across all participants, and that the greater the BMI prior to Ramadan fasting, the greater the weight loss. No significant differences were noted between genders. Weight loss was significant in the Middle East + North Africa, South Asia and South East Asia, but not in Westernized countries. Ramadan fasting promoted a transient reduction in fat mass as a percentage of weight, and absolute fat mass, but quickly returned to pre-fasting levels at follow-up 2-5 weeks later. A significant reduction in fat-free mass was also noted but 30% less than total fat mass. There was insufficient data to analysis the possible impact of physical activity. The authors conclude that Ramadan represents an opportunity for promoting weight and fat loss for people with overweight or obesity but requires strategies for long-term maintenance
Abstract
BACKGROUND Ramadan involves one month of fasting from sunrise to sunset. In this meta-analysis, we aimed to determine the effect of Ramadan fasting on weight and body composition. METHODS In May 2018, we searched six databases for publications that measured weight and body composition before and after Ramadan, and that did not attempt to influence physical activity or diet. RESULTS Data were collected from 70 publications (90 comparison groups, 2947 participants). There was a significant positive correlation between starting body mass index and weight lost during the fasting period. Consistently, there was a significant reduction in fat percentage between pre-Ramadan and post-Ramadan in people with overweight or obesity (-1.46 (95% confidence interval: -2.57 to -0.35) %, p = 0.010), but not in those of normal weight (-0.41 (-1.45 to 0.63) %, p = 0.436). Loss of fat-free mass was also significant between pre-Ramadan and post-Ramadan, but was about 30% less than loss of absolute fat mass. At 2⁻5 weeks after the end of Ramadan, there was a return towards, or to, pre-Ramadan measurements in weight and body composition. CONCLUSIONS Even with no advice on lifestyle changes, there are consistent-albeit transient-reductions in weight and fat mass with the Ramadan fast, especially in people with overweight or obesity.
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Effect of probiotics on lipid profiles and blood pressure in patients with type 2 diabetes: A meta-analysis of RCTs.
He, J, Zhang, F, Han, Y
Medicine. 2017;96(51):e9166
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Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder worldwide. Though many clinical studies have explored the effects of probiotics on T2DM they have concluded mixed results. The purpose of this meta-analysis was to evaluate all current randomised controlled trials and determine the effect of probiotics on lipid profiles and blood pressure in patients with T2DM. According to the existing literature, probiotic supplementation for patients with T2DM has a positive effect by lowering total cholesterol and increasing high-density lipoproteins (HDLs). While these beneficial effects on lipid profiles and blood pressure have been found, the authors conclude there is still a need for a multi-centre, longitudinal study to better understand the effects of probiotics on patients with T2DM.
Abstract
BACKGROUND This meta-analysis aimed to systematically evaluate the effects of probiotics on blood lipid and blood pressure among patients with type 2 diabetes mellitus (T2DM) based on the randomized controlled studies. METHODS PubMed, Cochrane, Embase, Wanfang, China National Knowledge Infrastructure, and VIP database were searched by the index words to identify the qualified randomized control trial. The latest research was done in the January 2017. Mean difference (MD) along with 95% confidence interval (CI) was used to analyze the included outcomes. RESULTS Ten trials were included at last with 297 patients in the treatment group and 294 patients in the control group. Probiotics significantly decreased the value of total cholesterol (SMD -0.57, 95% CI -0.92 to 0.21), triglyceride (SMD -0.66, 95% CI -0.93 to 0.39), low-density lipoprotein (SMD -0.40, 95% CI -0.79 to 0.01), systolic blood pressure (WMD -5.04, 95% CI -8.8 to 1.20), diastolic blood pressure (SMD -0.39, 95% CI -0.62 to 0.17), fasting blood glucose (FBG) (SMD 3.54, 95% CI 1.94-5.15) compared with the placebo treatment. Apart from this, probiotics could significantly improve the value of high-density lipoprotein (SMD 0.38, 95% CI 0.03-0.73). CONCLUSION Probiotics may decrease the indexes of lipid profile, blood pressure, and FBG in patients with T2DM; application of probiotics might be a new method for lipid profiles and blood pressure management in T2DM.
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Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis.
Ma, C, Avenell, A, Bolland, M, Hudson, J, Stewart, F, Robertson, C, Sharma, P, Fraser, C, MacLennan, G
BMJ (Clinical research ed.). 2017;359:j4849
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Obesity is known to increase the risk of many diseases including cardiovascular disease, various cancers and type 2 diabetes. Interestingly, there is evidence suggesting weight loss in obese adults may be harmful, particularly in older people with cardiovascular disease. The aim of this systematic review was to assess the effect of weight loss interventions for adults with obesity on mortality, cardiovascular disease, cancer and body weight. Based on the 30,000 participants identified, current evidence shows that weight loss interventions significantly decrease all cause mortality. There was also evidence to suggest weight loss is associated with developing new cardiovascular events, though fewer trials reported these outcomes so uncertainty remains around these results. Based on the current literature and this review, the authors conclude weight-reducing diets may reduce all cause mortality in adults with obesity and support public health measures to prevent weight gain and facilitate weight loss.
Abstract
Objective To assess whether weight loss interventions for adults with obesity affect all cause, cardiovascular, and cancer mortality, cardiovascular disease, cancer, and body weight.Design Systematic review and meta-analysis of randomised controlled trials (RCTs) using random effects, estimating risk ratios, and mean differences. Heterogeneity investigated using Cochran's Q and I2 statistics. Quality of evidence assessed by GRADE criteria.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, and full texts in our trials' registry for data not evident in databases. Authors were contacted for unpublished data.Eligibility criteria for selecting studies RCTs of dietary interventions targeting weight loss, with or without exercise advice or programmes, for adults with obesity and follow-up ≥1 year.Results 54 RCTs with 30 206 participants were identified. All but one trial evaluated low fat, weight reducing diets. For the primary outcome, high quality evidence showed that weight loss interventions decrease all cause mortality (34 trials, 685 events; risk ratio 0.82, 95% confidence interval 0.71 to 0.95), with six fewer deaths per 1000 participants (95% confidence interval two to 10). For other primary outcomes moderate quality evidence showed an effect on cardiovascular mortality (eight trials, 134 events; risk ratio 0.93, 95% confidence interval 0.67 to 1.31), and very low quality evidence showed an effect on cancer mortality (eight trials, 34 events; risk ratio 0.58, 95% confidence interval 0.30 to 1.11). Twenty four trials (15 176 participants) reported high quality evidence on participants developing new cardiovascular events (1043 events; risk ratio 0.93, 95% confidence interval 0.83 to 1.04). Nineteen trials (6330 participants) provided very low quality evidence on participants developing new cancers (103 events; risk ratio 0.92, 95% confidence interval 0.63 to 1.36).Conclusions Weight reducing diets, usually low in fat and saturated fat, with or without exercise advice or programmes, may reduce premature all cause mortality in adults with obesity.Systematic review registration PROSPERO CRD42016033217.
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Therapist-supported Internet cognitive behavioural therapy for anxiety disorders in adults.
Olthuis, JV, Watt, MC, Bailey, K, Hayden, JA, Stewart, SH
The Cochrane database of systematic reviews. 2016;3:CD011565
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Previous research has supported the use of cognitive behavioural therapy (CBT) in the treatment of anxiety disorders, which is aimed at changing negative or unhealthy thinking patterns. Many individuals with anxiety find it challenging to get to CBT appointments and so an internet-based programme, with telephone and email support, has been developed. This systematic review of 38 randomised controlled trial studies aimed to assess the effects of internet CBT (ICBT) on anxiety symptoms and severity. The results showed that there was a clinically important improvement in anxiety alongside reductions in symptom severity and an increase in the patient’s quality of life (QoL) when following ICBT compared to no treatment or online support group discussions. When comparing supported ICBT and self-guided CBT there were no differences between anxiety symptom severity and QoL. When comparing ICBT and face to face therapist-supported CBT, no differences were reported in anxiety symptoms and QoL. It was concluded that ICBT is more beneficial than no treatment or online discussion groups and may be just as useful as face-to-face CBT. The number of studies that compared ICBT to self-guided CBT was limited and so specific conclusions were difficult to ascertain. This study could be used by healthcare professionals to understand that people suffering from anxiety may not be receiving the treatment they need for fears of new situations or leaving the house. In this instance ICBT is an alternative treatment that is just as beneficial as face-to-face therapy.
Abstract
BACKGROUND Cognitive behavioural therapy (CBT) is an evidence-based treatment for anxiety disorders. Many people have difficulty accessing treatment, due to a variety of obstacles. Researchers have therefore explored the possibility of using the Internet to deliver CBT; it is important to ensure the decision to promote such treatment is grounded in high quality evidence. OBJECTIVES To assess the effects of therapist-supported Internet CBT (ICBT) on remission of anxiety disorder diagnosis and reduction of anxiety symptoms in adults as compared to waiting list control, unguided CBT, or face-to-face CBT. Effects of treatment on quality of life and patient satisfaction with the intervention were also assessed. SEARCH METHODS We searched the Cochrane Depression, Anxiety and Neurosis Review Group Specialised Register (CCDANCTR) to 16 March 2015. The CCDANCTR includes relevant randomised controlled trials from MEDLINE, EMBASE, PsycINFO and CENTRAL. We also searched online clinical trial registries and reference lists of included studies. We contacted authors to locate additional trials. SELECTION CRITERIA Each identified study was independently assessed for inclusion by two authors. To be included, studies had to be randomised controlled trials of therapist-supported ICBT compared to a waiting list, attention, information, or online discussion group; unguided CBT (that is, self-help); or face-to-face CBT. We included studies that treated adults with an anxiety disorder (panic disorder, agoraphobia, social phobia, post-traumatic stress disorder, acute stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and specific phobia) defined according to the Diagnostic and Statistical Manual of Mental Disorders III, III-R, IV, IV-TR or the International Classification of Disesases 9 or 10. DATA COLLECTION AND ANALYSIS Two authors independently assessed the risk of bias of included studies and judged overall study quality. We used data from intention-to-treat analyses wherever possible. We assessed treatment effect for the dichotomous outcome of clinically important improvement in anxiety using a risk ratio (RR) with 95% confidence interval (CI). For disorder-specific and general anxiety symptom measures and quality of life we assessed continuous scores using standardized mean differences (SMD). We examined statistical heterogeneity using the I(2) statistic. MAIN RESULTS We screened 1736 citations and selected 38 studies (3214 participants) for inclusion. The studies examined social phobia (11 trials), panic disorder with or without agoraphobia (8 trials), generalized anxiety disorder (5 trials), post-traumatic stress disorder (2 trials), obsessive compulsive disorder (2 trials), and specific phobia (2 trials). Eight remaining studies included a range of anxiety disorder diagnoses. Studies were conducted in Sweden (18 trials), Australia (14 trials), Switzerland (3 trials), the Netherlands (2 trials), and the USA (1 trial) and investigated a variety of ICBT protocols. Three primary comparisons were identified, therapist-supported ICBT versus waiting list control, therapist-supported versus unguided ICBT, and therapist-supported ICBT versus face-to-face CBT.Low quality evidence from 11 studies (866 participants) contributed to a pooled risk ratio (RR) of 3.75 (95% CI 2.51 to 5.60; I(2) = 50%) for clinically important improvement in anxiety at post-treatment, favouring therapist-supported ICBT over a waiting list, attention, information, or online discussion group only. The SMD for disorder-specific symptoms at post-treatment (28 studies, 2147 participants; SMD -1.06, 95% CI -1.29 to -0.82; I(2) = 83%) and general anxiety symptoms at post-treatment (19 studies, 1496 participants; SMD -0.75, 95% CI -0.98 to -0.52; I(2) = 78%) favoured therapist-supported ICBT; the quality of the evidence for both outcomes was low.One study compared unguided CBT to therapist-supported ICBT for clinically important improvement in anxiety at post-treatment, showing no difference in outcome between treatments (54 participants; very low quality evidence). At post-treatment there were no clear differences between unguided CBT and therapist-supported ICBT for disorder-specific anxiety symptoms (5 studies, 312 participants; SMD -0.22, 95% CI -0.56 to 0.13; I(2) = 58%; very low quality evidence) or general anxiety symptoms (2 studies, 138 participants; SMD 0.28, 95% CI -2.21 to 2.78; I(2) = 0%; very low quality evidence).Compared to face-to-face CBT, therapist-supported ICBT showed no significant differences in clinically important improvement in anxiety at post-treatment (4 studies, 365 participants; RR 1.09, 95% CI 0.89 to 1.34; I(2) = 0%; low quality evidence). There were also no clear differences between face-to-face and therapist supported ICBT for disorder-specific anxiety symptoms at post-treatment (7 studies, 450 participants; SMD 0.06, 95% CI -0.25 to 0.37; I(2) = 60%; low quality evidence) or general anxiety symptoms at post-treatment (5 studies, 317 participants; SMD 0.17, 95% CI -0.35 to 0.69; I(2) = 78%; low quality evidence).Overall, risk of bias in included studies was low or unclear for most domains. However, due to the nature of psychosocial intervention trials, blinding of participants and personnel, and outcome assessment tended to have a high risk of bias. Heterogeneity across a number of the meta-analyses was substantial, some was explained by type of anxiety disorder or may be meta-analytic measurement artefact due to combining many assessment measures. Adverse events were rarely reported. AUTHORS' CONCLUSIONS Therapist-supported ICBT appears to be an efficacious treatment for anxiety in adults. The evidence comparing therapist-supported ICBT to waiting list, attention, information, or online discussion group only control was low to moderate quality, the evidence comparing therapist-supported ICBT to unguided ICBT was very low quality, and comparisons of therapist-supported ICBT to face-to-face CBT were low quality. Further research is needed to better define and measure any potential harms resulting from treatment. These findings suggest that therapist-supported ICBT is more efficacious than a waiting list, attention, information, or online discussion group only control, and that there may not be a significant difference in outcome between unguided CBT and therapist-supported ICBT; however, this latter finding must be interpreted with caution due to imprecision. The evidence suggests that therapist-supported ICBT may not be significantly different from face-to-face CBT in reducing anxiety. Future research should explore heterogeneity among studies which is reducing the quality of the evidence body, involve equivalence trials comparing ICBT and face-to-face CBT, examine the importance of the role of the therapist in ICBT, and include effectiveness trials of ICBT in real-world settings. A timely update to this review is needed given the fast pace of this area of research.