Single-incision sling operations for urinary incontinence in women.

BACKGROUND: Stress urinary incontinence imposes a significant health and economic burden on individuals and society. Single-incision slings are a minimally-invasive treatment option for stress urinary incontinence. They involve passing a short synthetic device through the anterior vaginal wall to support the mid-urethra. The use of polypropylene mesh in urogynaecology, including mid-urethral slings, is restricted in many countries. This is a review update (previous search date 2012). OBJECTIVES: To assess the effects of single-incision sling operations for treating urinary incontinence in women, and to summarise the principal findings of relevant economic evaluations. SEARCH METHODS: We searched the Cochrane Incontinence Specialised Register, which contains trials identified from: CENTRAL, MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, and two trials registers. We handsearched journals, conference proceedings, and reference lists of relevant articles to 20 September 2022. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials in women with stress (or stress-predominant mixed) urinary incontinence in which at least one, but not all, trial arms included a single-incision sling. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The primary outcome was subjective cure or improvement of urinary incontinence. MAIN RESULTS: We included 62 studies with a total of 8051 women in this review. We did not identify any studies comparing single-incision slings to no treatment, conservative treatment, colposuspension, or laparoscopic procedures. We assessed most studies as being at low or unclear risk of bias, with five studies at high risk of bias for outcome assessment. Sixteen trials used TVT-Secur, a single-incision sling withdrawn from the market in 2013. The primary analysis in this review excludes trials using TVT-Secur. We report separate analyses for these trials, which did not substantially alter the effect estimates. We identified two cost-effectiveness analyses and one cost-minimisation analysis. Single-incision sling versus autologous fascial sling One study (70 women) compared single-incision slings to autologous fascial slings. It is uncertain if single-incision slings have any effect on risk of dyspareunia (painful sex) or mesh exposure, extrusion or erosion compared with autologous fascial slings. Subjective cure or improvement of urinary incontinence at 12 months, patient-reported pain at 24 months or longer, number of women with urinary retention, quality of life at 12 months and the number of women requiring repeat continence surgery or sling revision were not reported for this comparison. Single-incision sling versus retropubic sling Ten studies compared single-incision slings to retropubic slings. There may be little to no difference between single-incision slings and retropubic slings in subjective cure or improvement of incontinence at 12 months (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.91 to 1.07; 2 trials, 297 women; low-certainty evidence). It is uncertain whether single-incision slings increase the risk of mesh exposure, extrusion or erosion compared with retropubic minimally-invasive slings; the wide confidence interval is consistent with both benefit and harm (RR 1.55, 95% CI 0.24 to 9.82; 3 trials, 267 women; low-certainty evidence). It is uncertain whether single-incision slings lead to fewer women having postoperative urinary retention compared with retropubic slings; the wide confidence interval is consistent with possible benefit and harm (RR 0.47, 95% CI 0.12 to 1.84; 2 trials, 209 women; low-certainty evidence). The effect of single-incision slings on the risk of repeat continence surgery or mesh revision compared with retropubic slings is uncertain (RR 4.19, 95% CI 0.31 to 57.28; 2 trials, 182 women; very low-certainty evidence). One study reported quality of life, but not in a suitable format for analysis. Patient-reported pain at more than 24 months and the number of women with dyspareunia were not reported for this comparison. We downgraded the evidence due to concerns about risks of bias, imprecision and inconsistency. Single-incision sling versus transobturator sling Fifty-one studies compared single-incision slings to transobturator slings. The evidence ranged from high to low certainty. There is no evidence of a difference in subjective cure or improvement of incontinence at 12 months when comparing single-incision slings with transobturator slings (RR 1.00, 95% CI 0.97 to 1.03; 17 trials, 2359 women; high-certainty evidence). Single-incision slings probably have a reduced risk of patient-reported pain at 24 months post-surgery compared with transobturator slings (RR 0.12, 95% CI 0.02 to 0.68; 2 trials, 250 women; moderate-certainty evidence). The effect of single-incision slings on the risk of dyspareunia is uncertain compared with transobturator slings, as the wide confidence interval is consistent with possible benefit and possible harm (RR 0.78, 95% CI 0.41 to 1.48; 8 trials, 810 women; moderate-certainty evidence). There are a similar number of mesh exposures, extrusions or erosions with single-incision slings compared with transobturator slings (RR 0.61, 95% CI 0.39 to 0.96; 16 trials, 2378 women; high-certainty evidence). Single-incision slings probably result in similar or reduced cases of postoperative urinary retention compared with transobturator slings (RR 0.68, 95% CI 0.47 to 0.97; 23 trials, 2891 women; moderate-certainty evidence). Women with single-incision slings may have lower quality of life at 12 months compared to transobturator slings (standardised mean difference (SMD) 0.24, 95% CI 0.09 to 0.39; 8 trials, 698 women; low-certainty evidence). It is unclear whether single-incision slings lead to slightly more women requiring repeat continence surgery or mesh revision compared with transobturator slings (95% CI consistent with possible benefit and harm; RR 1.42, 95% CI 0.94 to 2.16; 13 trials, 1460 women; low-certainty evidence). We downgraded the evidence due to indirectness, imprecision and risks of bias. AUTHORS' CONCLUSIONS: Single-incision sling operations have been extensively researched in randomised controlled trials. They may be as effective as retropubic slings and are as effective as transobturator slings for subjective cure or improvement of stress urinary incontinence at 12 months. It is uncertain if single-incision slings lead to better or worse rates of subjective cure or improvement compared with autologous fascial slings. There are still uncertainties regarding adverse events and longer-term outcomes. Therefore, longer-term data are needed to clarify the safety and long-term effectiveness of single-incision slings compared to other mid-urethral slings.

Vitamin and mineral supplementation for maintaining cognitive function in cognitively healthy people in mid and late life.

BACKGROUND: Vitamins and minerals play multiple functions within the central nervous system which may help to maintain brain health and optimal cognitive functioning. Supplementation of the diet with various vitamins and minerals has been suggested as a means of maintaining cognitive function, or even of preventing dementia, in later life. OBJECTIVES: To evaluate the effects of vitamin and mineral supplementation on cognitive function in cognitively healthy people aged 40 years or more. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's (CDCIG) specialised register, as well as MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov and the WHO Portal/ICTRP from inception to 26th January 2018. SELECTION CRITERIA: We included randomised controlled trials that evaluated the cognitive effects on people aged 40 years or more of any vitamin or mineral supplements taken by mouth for at least three months. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, and quality assessments were done in duplicate. Vitamins were considered broadly in the categories of B vitamins, antioxidant vitamins, and combinations of both. Minerals were considered separately, where possible. If interventions and outcomes were considered sufficiently similar, then data were pooled. In order to separate short-term cognitive effects from possible longer-term effects on the trajectory of cognitive decline, data were pooled for various treatment durations from 3 months to 12 months and up to 10 years or more. MAIN RESULTS: In total, we included 28 studies with more than 83,000 participants. There were some general limitations of the evidence. Most participants were enrolled in studies which were not designed primarily to assess cognition. These studies often had no baseline cognitive assessment and used only brief cognitive assessments at follow-up. Very few studies assessed the incidence of dementia. Most study reports did not mention adverse events or made only very general statements about them. Only 10 studies had a mean follow-up > 5 years. Only two studies had participants whose mean age was < 60 years at baseline. The risk of bias in the included studies was generally low, other than a risk of attrition bias for longer-term outcomes. We considered the certainty of the evidence behind almost all results to be moderate or low.We included 14 studies with 27,882 participants which compared folic acid, vitamin B12, vitamin B6, or a combination of these to placebo. The majority of participants were aged over 60 years and had a history of cardio- or cerebrovascular disease. We found that giving B vitamin supplements to cognitively healthy adults, mainly in their 60s and 70s, probably has little or no effect on global cognitive function at any time point up to 5 years (SMD values from -0.03 to 0.06) and may also have no effect at 5-10 years (SMD -0.01). There were very sparse data on adverse effects or on incidence of cognitive impairment or dementia.We included 8 studies with 47,840 participants in which the active intervention was one or more of the antioxidant vitamins: ß-carotene, vitamin C or vitamin E. Results were mixed. For overall cognitive function, there was low-certainty evidence of benefit associated with ß-carotene after a mean of 18 years of treatment (MD 0.18 TICS points, 95% CI 0.01 to 0.35) and of vitamin C after 5 years to 10 years (MD 0.46 TICS points, 95% CI 0.14 to 0.78), but not at earlier time points. From two studies which reported on dementia incidence, there was low-certainty evidence of no effect of an antioxidant vitamin combination or of vitamin E, either alone or combined with selenium. One of the included studies had been designed to look for effects on the incidence of prostate cancer; it found a statistically significant increase in prostate cancer diagnoses among men taking vitamin E.One trial with 4143 participants compared vitamin D3 (400 IU/day) and calcium supplements to placebo. We found low- to moderate-certainty evidence of no effect of vitamin D3 and calcium supplements at any time-point up to 10 years on overall cognitive function (MD after a mean of 7.8 years -0.1 MMSE points, 95% CI -0.81 to 0.61) or the incidence of dementia (HR 0.94, 95% CI 0.72 to 1.24). A pilot study with 60 participants used a higher dose of vitamin D3 (4000 IU on alternate days) and found preliminary evidence that this dose probably has no effect on cognitive function over six months.We included data from one trial of zinc and copper supplementation with 1072 participants. There was moderate-certainty evidence of little or no effect on overall cognitive function (MD 0.6 MMSE points, 95% CI -0.19 to 1.39) or on the incidence of cognitive impairment after 5 years to 10 years. A second smaller trial provided no usable data, but reported no cognitive effects of six months of supplementation with zinc gluconate.From one study with 3711 participants, there was low-certainty evidence of no effect of approximately five years of selenium supplementation on the incidence of dementia (HR 0.83, 95% CI 0.61 to 1.13).Finally, we included three trials of complex supplements (combinations of B vitamins, antioxidant vitamins, and minerals) with 6306 participants. From the one trial which assessed overall cognitive function, there was low-certainty evidence of little or no effect on the TICS (MD after a mean of 8.5 years 0.12, 95% CI -0.14 to 0.38). AUTHORS' CONCLUSIONS: We did not find evidence that any vitamin or mineral supplementation strategy for cognitively healthy adults in mid or late life has a meaningful effect on cognitive decline or dementia, although the evidence does not permit definitive conclusions. There were very few data on supplementation starting in midlife (< 60 years); studies designed to assess cognitive outcomes tended to be too short to assess maintenance of cognitive function; longer studies often had other primary outcomes and used cognitive measures which may have lacked sensitivity. The only positive signals of effect came from studies of long-term supplementation with antioxidant vitamins. These may be the most promising for further research.

Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment.

BACKGROUND: Vitamins and minerals have many functions in the nervous system which are important for brain health. It has been suggested that various different vitamin and mineral supplements might be useful in maintaining cognitive function and delaying the onset of dementia. In this review, we sought to examine the evidence for this in people who already had mild cognitive impairment (MCI). OBJECTIVES: To evaluate the effects of vitamin and mineral supplementation on cognitive function and the incidence of dementia in people with mild cognitive impairment. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's (CDCIG) specialised register, as well as MEDLINE, Embase, PsycINFO, CENTRAL, CINAHL, LILACs, Web of Science Core Collection, ClinicalTrials.gov, and the WHO Portal/ICTRP, from inception to 25 January 2018. SELECTION CRITERIA: We included randomised or quasi-randomised, placebo-controlled trials which evaluated orally administered vitamin or mineral supplements in participants with a diagnosis of mild cognitive impairment and which assessed the incidence of dementia or cognitive outcomes, or both. We were interested in studies applicable to the general population of older people and therefore excluded studies in which participants had severe vitamin or mineral deficiencies. DATA COLLECTION AND ANALYSIS: We sought data on our primary outcomes of dementia incidence and overall cognitive function and on secondary outcomes of episodic memory, executive function, speed of processing, quality of life, functional performance, clinical global impression, adverse events, and mortality. We conducted data collection and analysis according to standard Cochrane systematic review methods. We assessed the risk of bias of included studies using the Cochrane 'Risk of bias' assessment tool. We grouped vitamins and minerals according to their putative mechanism of action and, where we considered it to be clinically appropriate, we pooled data using random-effects methods. We used GRADE methods to assess the overall quality of evidence for each comparison and outcome. MAIN RESULTS: We included five trials with 879 participants which investigated B vitamin supplements. In four trials, the intervention was a combination of vitamins B6, B12, and folic acid; in one, it was folic acid only. Doses varied. We considered there to be some risks of performance and attrition bias and of selective outcome reporting among these trials. Our primary efficacy outcomes were the incidence of dementia and scores on measures of overall cognitive function. None of the trials reported the incidence of dementia and the evidence on overall cognitive function was of very low-quality. There was probably little or no effect of B vitamins taken for six to 24 months on episodic memory, executive function, speed of processing, or quality of life. The evidence on our other secondary clinical outcomes, including harms, was very sparse or very low-quality. There was evidence from one study that there may be a slower rate of brain atrophy over two years in participants taking B vitamins. The same study reported subgroup analyses based on the level of serum homocysteine (tHcy) at baseline and found evidence that B vitamins may improve episodic memory in those with tHcy above the median at baseline.We included one trial (n = 516) of vitamin E supplementation. Vitamin E was given as 1000 IU of alpha-tocopherol twice daily. We considered this trial to be at risk of attrition and selective reporting bias. There was probably no effect of vitamin E on the probability of progression from MCI to Alzheimer's dementia over three years (HR 1.02; 95% CI 0.74 to 1.41; n = 516; 1 study, moderate-quality evidence). There was also no evidence of an effect at intermediate time points. The available data did not allow us to conduct analyses, but the authors reported no significant effect of three years of supplementation with vitamin E on overall cognitive function, episodic memory, speed of processing, clinical global impression, functional performance, adverse events, or mortality (five deaths in each group). We considered this to be low-quality evidence.We included one trial (n = 256) of combined vitamin E and vitamin C supplementation and one trial (n = 26) of supplementation with chromium picolinate. In both cases, there was a single eligible cognitive outcome, but we considered the evidence to be very low-quality and so could not be sure of any effects. AUTHORS' CONCLUSIONS: The evidence on vitamin and mineral supplements as treatments for MCI is very limited. Three years of treatment with high-dose vitamin E probably does not reduce the risk of progression to dementia, but we have no data on this outcome for other supplements. Only B vitamins have been assessed in more than one RCT. There is no evidence for beneficial effects on cognition of supplementation with B vitamins for six to 24 months. Evidence from a single study of a reduced rate of brain atrophy in participants taking vitamin B and a beneficial effect of vitamin B on episodic memory in those with higher tHcy at baseline warrants attempted replication.