Overweight or obesity increases the risk of cardiovascular disease among older Australian adults, even in the absence of cardiometabolic risk factors: a Bayesian survival analysis from the Hunter Community Study.

OBJECTIVE: To estimate the risk of cardiovascular disease (CVD) in older adults with overweight or obesity without metabolic risk factors using a Bayesian survival analysis. DESIGN: Prospective cohort study with median follow-up of 9.7 years. SETTING: Newcastle, New South Wales, Australia. PARTICIPANTS: A total of 2313 community-dwelling older men and women. INTERVENTION/EXPOSURE: Participants without known CVD and with a body mass index (BMI) ≥ 18.5 kg m2 were stratified by BMI and metabolic risk to create six BMI-metabolic health categories. Metabolic risk was defined according to the International Diabetes Federation criteria for metabolic syndrome. 'Metabolically healthy' was defined as absence of metabolic risk factors. Bayesian survival analysis, incorporating prior information from a previously published meta-analysis was used to assess the effect of BMI-metabolic health categories on time from recruitment to CVD. MAIN OUTCOME: Incident physician-diagnosed CVD, defined as fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, angina, or coronary revascularisation procedure, was determined by linkage to hospital admissions records and Medicare Australia data. Secondary outcomes were cardiovascular mortality and all-cause mortality. RESULTS: From 2313 adults with complete metabolic health data over a median follow-up of 9.7 years, 283 incident CVD events, 58 CVD related deaths and 277 deaths from any cause occurred. In an adjusted Bayesian survival model of complete cases with informative prior and metabolically healthy normal weight as the reference group, the risk of CVD was increased in metabolically healthy overweight (HR = 1.52, 95% credible interval 0.96-2.36), and in metabolically healthy obesity (HR = 1.86, 95% credible interval 1.14-3.08). Imputation of missing metabolic health and confounding data did not change the results. CONCLUSION: There was increased risk of CVD in older adults with overweight or obesity, even in the absence of any metabolic abnormality. This argues against the notion of 'metabolically healthy' overweight or obesity.

The effect of zinc supplementation on glucose homeostasis: a randomised double-blind placebo-controlled trial.

AIMS: The burden and health costs of Type 2 Diabetes Mellitus continue to increase globally and prevention strategies in at-risk people need to be explored. Previous work, in both animal models and humans, supports the role of zinc in improving glucose homeostasis. We, therefore, aimed to test the effectiveness of zinc supplementation on glycaemic control in pre-diabetic adults. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across 10 General Practitioner (GP) practices in NSW, Australia. The trial is known as Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD)Study. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4%, 39-46 mmol/mol) men and women (N = 98) were all assigned to a free state government telephone health coaching service (New South Wales Get Healthy Information and Coaching Service) and then randomised to either daily 30 mg zinc gluconate or placebo. Blood tests were collected at baseline, 1, 6 and 12 months for the primary outcomes (HbA1c, fasting blood glucose (FBG)); secondary outcomes included Homeostasis Model Assessment 2 (HOMA 2) parameters, lipids, body weight, height, waist circumference, blood pressure and pulse. RESULTS: The baseline-adjusted mean group difference at 6 months, expressed as treatment-placebo, (95% CI) was -0.02 (-0.14, 0.11, p = 0.78) for HbA1c and 0.17 (-0.07, 0.42; p = 0.17) for FBG, neither of which were statistically significant. There were also no significant differences between groups in any of the secondary outcomes. Zinc was well tolerated, and compliance was high (88%). CONCLUSION: We believe our results are consistent with other Western clinical trial studies and do not support the use of supplemental zinc in populations with a Western diet. There may still be a role for supplemental zinc in the developing world where diets may be zinc deficient. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.

Association between plasma phospholipid omega-3 polyunsaturated fatty acids and type 2 diabetes is sex dependent: The Hunter Community Study.

BACKGROUND & AIMS: Chronic inflammation drives the development of insulin resistance and type 2 diabetes. Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) eicosapentaenoic acid (EPA, c20:5n-3) and docosahexaenoic acid (DHA, c22:6n-3) may protect against type 2 diabetes development. The aim of this current study is to determine whether LCn-3PUFA status is associated with type 2 diabetes in the Hunter Community Study. METHODS: Men and women aged 55-85 years were randomly selected from the electoral roll and invited to participate. Participants were included in the current study if they had plasma phospholipid fatty acid composition data available and diabetes status could be determined. LCn-3PUFA status was determined by fatty acid composition of plasma phospholipids (EPA + DHA, %,w/w). Diabetes was determined according to World Health Organisation criteria. Insulin was measured in n = 251 participants and HOMA-IR calculated. RESULTS: In total, n = 2092 (diabetes: n = 249) participants were included. After adjusting for confounders of diabetes, LCn-3PUFA status was inversely associated with diabetes in overweight/obese females (OR [95%CI]: 0.90 [0.80, 1.00], p = 0.045) but not males (p-interactionsex = 0.041). Overweight/obese females with diabetes had significantly lower levels of DHA than those without diabetes (mean difference [95%CI]: -0.53 [-0.87, -0.20], p = 0.002), with no difference in EPA. LCn-3PUFA was inversely associated with HOMA-IR (r = -0.175, p = 0.005). CONCLUSIONS: This study provides further evidence of a sex-dependent association between LCn-3PUFA and type 2 diabetes. Causal pathways between LCn-3PUFA and type 2 diabetes merits delineation.

Long-chain omega-3 polyunsaturated fatty acids and cognitive decline in non-demented adults: a systematic review and meta-analysis.

CONTEXT: Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) are widely considered as nootropic agents that may be beneficial in reversing cognitive impairment. OBJECTIVE: The present systematic review of randomized controlled trials was conducted to determine the changes in cognitive function after intervention with LCn-3PUFA supplementation in non-demented adults, including those with mild cognitive impairment. DATA SOURCES: Five databases (MEDLINE, CINAHL, Scopus, EMBASE, and the Cochrane Library) were searched systematically along with reference lists of selected articles. STUDY SELECTION: Studies were eligible for inclusion if they measured the effect of LCn-3PUFA supplementation on cognition in non-demented adults. DATA EXTRACTION: A total of 787 records were screened, of which 25 studies were eligible for inclusion. Treatment effects were summarized as global cognitive function for primary outcome and measured using the Mini-Mental State Examination and individual cognitive domains for secondary outcome. The pooled effect sizes were estimated using Hedge's g and random-effects modeling. DATA ANALYSIS: Results from randomized controlled trials indicate that LCn-3PUFAs have no effect on global cognitive function (Hedge's g = 0.02; 95% confidence interval, -0.12 to 0.154), and among the specific cognitive domains, only memory function showed a mild benefit (Hedge's g = 0.31; P = 0.003; z = 2.945). CONCLUSION: The existing literature suggests that LCn-3PUFA supplementation could provide a mild benefit in improving memory function in non-demented older adults. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42017078664.

Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD Study) - study protocol for a randomised placebo-controlled trial in Australia.

BACKGROUND: Diabetes is increasing in incidence, morbidity and treatment costs globally, hence prevention strategies need to be explored. Animal studies and some human data have shown that zinc can improve glycaemic control, but the impact of this effect in a pre-diabetic population remains uncertain. This study is designed to investigate whether zinc gluconate and lifestyle coaching can improve glucose handling and ultimately reduce diabetes incidence in an at-risk pre-diabetic population in Australia. METHODS/DESIGN: The study will be a randomised, placebo-controlled, double-blind clinical trial. The study will be conducted at the Hunter New England Local Health District New South Wales (NSW), Australia. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4) male and female participants (n = 410) aged 40-70 years will be recruited through the Diabetes Alliance Network, a collaboration of diabetes specialists and general practitioner practices. All participants will be given routine care to encourage healthy lifestyle changes using a telephone coaching service (Get Healthy Information and Coaching Service, NSW Health) and then randomised to receive a supplement, either zinc gluconate (equivalent to 30 mg of elemental zinc) or placebo of identical appearance for 12 months. The identity of the supplements will be blinded to both research personnel and the participants. Participants will be asked to complete medical, lifestyle and dietary surveys and will have baseline and final visits at their general practitioner practice. Primary outcomes will be HbA1c and insulin sensitivity collected at baseline and at 1, 6 and 12 months; secondary outcomes will include fasting blood glucose, fasting cholesterol, blood pressure and body mass index. The primary efficacy endpoint will be judged at 6 months. DISCUSSION: This study will generate new evidence about the potential for health coaching, with or without zinc supplementation, to improve glucose handling and ultimately to reduce progression from pre-diabetes to diabetes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268 . Registered on 6 July 2018.

Calcium and Vitamin D Supplementation for Prevention of Preeclampsia: A Systematic Review and Network Meta-Analysis.

Vitamin D supplementation effects with or without calcium in pregnancy for reducing risk of preeclampsia and gestational or pregnancy induced hypertension are controversial. Literature was systematically searched in Medline, Scopus and Cochrane databases from inception to July 2017. Only randomized controlled trials (RCTs) in English were selected if they had any pair of interventions (calcium, vitamin D, both, or placebo). Systematic review with two-step network-meta-analysis was used to indirectly estimate supplementary effects. Twenty-seven RCTs with 28,000 women were eligible. A direct meta-analysis suggested that calcium, vitamin D, and calcium plus vitamin D could lower risk of preeclampsia when compared to placebo with the pooled risk ratios (RRs) of 0.54 (0.41, 0.70), 0.47 (0.24, 0.89) and 0.50 (0.32, 0.78), respectively. Results of network meta-analysis were similar with the corresponding RRs of 0.49 (0.35, 0.69), 0.43 (0.17, 1.11), and 0.57 (0.30, 1.10), respectively. None of the controls were significant. Efficacy of supplementation, which was ranked by surface under cumulative ranking probabilities, were: vitamin D (47.4%), calcium (31.6%) and calcium plus vitamin D (19.6%), respectively. Calcium supplementation may be used for prevention for preeclampsia. Vitamin D might also worked well but further large scale RCTs are warranted to confirm our findings.

The efficacy of local infiltration analgesia in the early postoperative period after total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: Local infiltration analgesia (LIA) has emerged as an alternative treatment for postoperative pain after total knee arthroplasty (TKA). Its efficacy remains inconclusive with inconsistent results from previous studies and meta-analyses. There is no agreement on which local anaesthetic agent and infiltration technique is most effective and well tolerated. OBJECTIVE: The objective was to compare LIA after primary TKA with placebo or no infiltration in terms of early postoperative pain relief, mobilisation, length of hospital stay (LOS) and complications when used as a primary treatment or as an adjunct to regional anaesthesia. The role of injection sites, postoperative injection or infusion and multimodal drug injection with ketorolac were also explored. DESIGN: A systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: A literature search was performed using PubMed and SCOPUS up to September 2015. ELIGIBILITY CRITERIA: RCTs comparing LIA with placebo or no infiltration after primary TKA in terms of pain score and opioid consumption at 24 and 48 h, mobilisation, LOS and complications were included. RESULTS: In total 38 RCTs were included. LIA groups had lower pain scores, opioid consumption and postoperative nausea and vomiting, higher range of motion at 24 h and shorter LOS than no injection or placebo. After subgroup analysis, intraoperative peri-articular but not intra-articular injection had lower pain score at 24 h than no injection or placebo with the pooled mean difference of pain score at rest of -0.89 [95% CI (-1.40 to -0.38); I = 92.0%]. Continuing with postoperative injection or infusion reduced 24-h pain score with the pooled mean difference at rest of -1.50 [95% CI (-1.92 to -1.08); I = 60.5%]. There was no additional benefit in terms of pain relief during activity, opioid consumption, range of movement or LOS when LIA was used as an adjunct to regional anaesthesia. Four out of 735 patients receiving LIA reported deep knee infection, three of whom had had postoperative catheter placement. CONCLUSION: LIA is effective for acute pain management after TKA. Intraoperative peri-articular but not intra-articular injection may be helpful in pain control up to 24 h. The use of postoperative intra-articular catheter placement is still inconclusive. The benefit of LIA as an adjunctive treatment to regional anaesthesia was not demonstrated.

Zinc supplementation for improving glucose handling in pre-diabetes: A double blind randomized placebo controlled pilot study.

AIMS: There are a number of studies showing that zinc supplementation may improve glucose handling in people with established diabetes. We sought to investigate whether this zinc-dependent improvement in glucose handling could potentially be harnessed to prevent the progression of pre-diabetes to diabetes. In this double-blind randomized placebo-controlled trial, we determined participants' fasting blood glucose levels, (FBG) and Homeostasis Model Assessment (HOMA) parameters (beta cell function, insulin sensitivity and insulin resistance) at baseline and after 6 months of zinc supplementation. METHODS: The Bangladesh Institute of Health Sciences Hospital (BIHS) (Mirpur, Dhaka, Bangladesh) database was used to identify 224 patients with prediabetes, of whom 55 met the inclusion criteria and agreed to participate. The participants were randomized either to the intervention or control group using block randomization. The groups received either 30mg zinc sulphate dispersible tablet or placebo, once daily for six months. RESULTS: After six months, the intervention group significantly improved their FBG concentration compared to the placebo group (5.37±0.20mmol/L vs 5.69±0.26, p<0.001) as well as compared to their own baseline (5.37±0.20mmol/L vs 5.8±0.09, p<0.001). Beta cell function, insulin sensitivity and insulin resistance all showed a statistically significant improvement as well. CONCLUSION: To our knowledge this is the first trial to show an improvement in glucose handling using HOMA parameters in participants with prediabetes. Larger randomized controlled trials are warranted to confirm these findings and to explore clinical endpoints.

Inflammation mediates the association between fatty acid intake and depression in older men and women.

Antioxidants and fatty acids are associated with depression and inflammation, and inflammation appears to predict depression risk; hence, the associations between these nutrients and depression may be mediated by inflammation. We hypothesized that inflammatory markers interleukin (IL)-6 and C-reactive protein (CRP) mediate the associations between antioxidant and fatty acid intakes, and depression. Participants were from the Hunter Community Study, a longitudinal cohort of adults aged 55-85 years. Dietary intake was assessed using the Older Australian's Food Frequency Questionnaire. Fasting blood samples were drawn for analysis of nutrient and inflammatory biomarkers. Depressive symptoms were assessed using the 20-item Center for Epidemiologic Studies-Depression scale at baseline and at 5-year follow-up. Linear mixed models were used to investigate longitudinal associations between dietary intakes and depression, and mediation analyses were carried out to determine if IL-6 and/or CRP were the mediators. Analyses were conducted on men and women separately and adjusted for potential confounders. Fruit and monounsaturated fat intakes were negatively associated with depression, whereas total fat and saturated fat intakes were positively associated with depression in both sexes. Omega-3 polyunsaturated fat was inversely associated with depression in men only. IL-6 was a significant mediator of the association between fruits with low carotenoid content and depression in women. CRP significantly mediated the relationship between total fat, saturated fat, and monounsaturated fat intakes and depression in women, and saturated fat intake and depression in men. Our findings raise the possibility that the association between fatty acid intake and depression is partially mediated by inflammatory markers.

Macronutrient intake and type 2 diabetes risk in middle-aged Australian women. Results from the Australian Longitudinal Study on Women's Health.

OBJECTIVE: To investigate the association between macronutrient intake and type 2 diabetes risk in middle-aged Australian women. DESIGN: A prospective cohort study, with 6 years (2002-2007) of follow up. Dietary intake was assessed with a validated FFQ. Relative risks with 95 % confidence intervals were used to examine risk associations. SETTING: Australian Longitudinal Study on Women's Health, Australia. SUBJECTS: Australian women (n 8370) from the Australian Longitudinal Study on Women's Health aged 45-50 years and free of type 2 diabetes at baseline. RESULTS: After 6 years of follow-up, 311 women developed type 2 diabetes. After adjusting for sociodemographic, lifestyle and other dietary risk factors, MUFA, total n-3 PUFA, α-linolenic acid and total n-6 PUFA intakes were positively associated with the incidence of type 2 diabetes. The relative risks for type 2 diabetes for the highest compared with the lowest quintiles were 1·64 (95 % CI 1·06, 2·54), P = 0·04 for MUFA; 1·55 (95 % CI 1·03, 2·32), P = 0·01 for n-3 PUFA; 1·84 (95 % CI 1·25, 2·71), P < 0·01 for α-linolenic acid; and 1·60 (95 % CI 1·03, 2·48), P = 0·04 for n-6 PUFA. Other dietary macronutrients were not significantly associated with diabetes risk. CONCLUSIONS: The data indicate that consumption of MUFA, n-3 PUFA and n-6 PUFA may influence the risk of developing type 2 diabetes in women.

Is dietary zinc protective for type 2 diabetes? Results from the Australian longitudinal study on women's health.

BACKGROUND: Animal studies have shown that zinc intake has protective effects against type 2 diabetes, but few studies have been conducted to examine this relationship in humans. The aim of this study is to investigate if dietary zinc is associated with risk of type 2 diabetes in a longitudinal study of mid-age Australian women. METHODS: Data were collected from a cohort of women aged 45-50 years at baseline, participating in the Australian Longitudinal Study on Women's Health. A validated food frequency questionnaire was used to assess dietary intake and other nutrients. Predictors of 6-year incidence of type 2 diabetes were examined using multivariable logistic regression. RESULTS: From 8921 participants, 333 incident cases of type 2 diabetes were identified over 6 years of follow-up. After adjustment for dietary and non-dietary factors, the highest quintile dietary zinc intake had almost half the odds of developing type 2 diabetes (OR = 0.50, 95% C.I. 0.32-0.77) compared with the lowest quintile. Similar findings were observed for the zinc/iron ratio; the highest quintile had half the odds of developing type 2 diabetes (OR = 0.50, 95% C.I 0.30-0.83) after multivariable adjustment of covariates. CONCLUSIONS: Higher total dietary zinc intake and high zinc/iron ratio are associated with lower risk of type 2 diabetes in women. This finding is a positive step towards further research to determine if zinc supplementation may reduce the risk of developing type 2 diabetes.

Is serum zinc level associated with prediabetes and diabetes?: a cross-sectional study from Bangladesh.

AIMS: To determine serum zinc level and other relevant biological markers in normal, prediabetic and diabetic individuals and their association with Homeostasis Model Assessment (HOMA) parameters. METHODS: This cross-sectional study was conducted between March and December 2009. Any patient aged ≥ 30 years attending the medicine outpatient department of a medical university hospital in Dhaka, Bangladesh and who had a blood glucose level ordered by a physician was eligible to participate. RESULTS: A total of 280 participants were analysed. On fasting blood sugar results, 51% were normal, 13% had prediabetes and 36% had diabetes. Mean serum zinc level was lowest in prediabetic compared to normal and diabetic participants (mean differences were approximately 65 ppb/L and 33 ppb/L, respectively). In multiple linear regression, serum zinc level was found to be significantly lower in prediabetes than in those with normoglycemia. Beta cell function was significantly lower in prediabetes than normal participants. Adjusted linear regression for HOMA parameters did not show a statistically significant association between serum zinc level, beta cell function (P = 0.07) and insulin resistance (P = 0.08). Low serum zinc accentuated the increase in insulin resistance seen with increasing BMI. CONCLUSION: Participants with prediabetes have lower zinc levels than controls and zinc is significantly associated with beta cell function and insulin resistance. Further longitudinal population based studies are warranted and controlled trials would be valuable for establishing whether zinc supplementation in prediabetes could be a useful strategy in preventing progression to Type 2 diabetes.

The efficacy of zinc supplementation in depression: systematic review of randomised controlled trials.

BACKGROUND: Depression is a significant public health problem. Pre-clinical studies suggest a potential role of zinc in reducing or preventing depressive symptoms. Many epidemiological studies have examined the association of low zinc status with depression; however, clinical trials on the effect of zinc supplementation in depression are limited. This review aimed to synthesise results from all published randomised controlled trials on the efficacy of zinc supplementation for reducing or preventing depressive symptoms. METHODS: Six databases were searched over all years of records until March 2011. All randomised controlled trials with a comparison group, that examined zinc supplementation as the intervention and depressive symptoms as the primary outcome were included. Pairs of reviewers extracted key information of study characteristics and outcomes, and assessed the quality of each study. RESULTS: Four randomised controlled trials met inclusion criteria. In studies that examined the effects of zinc supplementation as an adjunct to antidepressants drug treatment, zinc significantly lowered depressive symptom scores of depressed patients. There is less clear evidence on the effectiveness of zinc supplementation alone on depressive symptoms of non-depressed healthy subjects. The overall study quality was rated 'moderate'. LIMITATIONS: There are limited trials examining the effects of zinc supplementation on depressive symptoms. An overall pooled estimate of effect for all included studies could not be calculated and evidence was difficult to summarise because of substantial heterogeneity. CONCLUSION: Evidence suggests potential benefits of zinc supplementation as a stand-alone intervention or as an adjunct to conventional antidepressant drug therapy for depression. However, there are methodological limitations in existing studies and so further well-designed, adequately powered research is required.

Spirituality, religion, social support and health among older Australian adults.

AIM: To examine the impact of perceived importance of spirituality or religion (ISR) and religious service attendance (RSA) on health and well-being in older Australians. METHODS: A cross-sectional survey of 752 community-dwelling men and women aged 55-85 years from the Hunter Region, New South Wales. RESULTS: Overall, 51% of participants felt spirituality or religion was important in their lives and 24% attended religious services at least 2-3 times a month. In univariate regression analyses, ISR and RSA were associated with increased levels of social support (P < 0.001). However, ISR was also associated with more comorbidities (incidence-rate ratio= 1.2, 95% confidence interval 1.08-1.33). There were no statistically significant associations between ISR or RSA and other measures such as mental and physical health. CONCLUSION: Spirituality and religious involvement have a beneficial impact on older Australians' perceptions of social support, and may enable individuals to better cope with the presence of multiple comorbidities later in life.

Management of chronic prostatitis/chronic pelvic pain syndrome: a systematic review and network meta-analysis.

CONTEXT: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, but trial evidence is conflicting and therapeutic options are controversial. OBJECTIVE: To conduct a systematic review and network meta-analysis comparing mean symptom scores and treatment response among α-blockers, antibiotics, anti-inflammatory drugs, other active drugs (phytotherapy, glycosaminoglycans, finasteride, and neuromodulators), and placebo. DATA SOURCES: We searched MEDLINE from 1949 and EMBASE from 1974 to November 16, 2010, using the PubMed and Ovid search engines. STUDY SELECTION: Randomized controlled trials comparing drug treatments in CP/CPPS patients. DATA EXTRACTION: Two reviewers independently extracted mean symptom scores, quality-of-life measures, and response to treatment between treatment groups. Standardized mean difference and random-effects methods were applied for pooling continuous and dichotomous outcomes, respectively. A longitudinal mixed regression model was used for network meta-analysis to indirectly compare treatment effects. DATA SYNTHESIS: Twenty-three of 262 studies identified were eligible. Compared with placebo, α-blockers were associated with significant improvement in symptoms with standardized mean differences in total symptom, pain, voiding, and quality-of-life scores of -1.7 (95% confidence interval [CI], -2.8 to -0.6), -1.1 (95% CI, -1.8 to -0.3), -1.4 (95% CI, -2.3 to -0.5), and -1.0 (95% CI, -1.8 to -0.2), respectively. Patients receiving α-blockers or anti-inflammatory medications had a higher chance of favorable response compared with placebo, with pooled RRs of 1.6 (95% CI, 1.1-2.3) and 1.8 (95% CI, 1.2-2.6), respectively. Contour-enhanced funnel plots suggested the presence of publication bias for smaller studies of α-blocker therapies. The network meta-analysis suggested benefits of antibiotics in decreasing total symptom scores (-9.8; 95% CI, -15.1 to -4.6), pain scores (-4.4; 95% CI, -7.0 to -1.9), voiding scores (-2.8; 95% CI, -4.1 to -1.6), and quality-of-life scores (-1.9; 95% CI, -3.6 to -0.2) compared with placebo. Combining α-blockers and antibiotics yielded the greatest benefits compared with placebo, with corresponding decreases of -13.8 (95% CI, -17.5 to -10.2) for total symptom scores, -5.7 (95% CI, -7.8 to -3.6) for pain scores, -3.7 (95% CI, -5.2 to -2.1) for voiding, and -2.8 (95% CI, -4.7 to -0.9) for quality-of-life scores. CONCLUSIONS: α-Blockers, antibiotics, and combinations of these therapies appear to achieve the greatest improvement in clinical symptom scores compared with placebo. Anti-inflammatory therapies have a lesser but measurable benefit on selected outcomes. However, beneficial effects of α-blockers may be overestimated because of publication bias.