Is There an Increased Risk of Post-Operative Surgical Site Infection after Orthopaedic Surgery in HIV Patients? A Systematic Review and Meta-Analysis

Background

There is dilemma as to whether patients infected with the Human Immunodeficiency Virus (HIV) requiring implant orthopaedic surgery are at an increased risk for post-operative surgical site infection (SSI). We conducted a systematic review to determine the effect of HIV on the risk of post-operative SSI and sought to determine if this risk is altered by antibiotic use beyond 24 hours.

Methods

We searched electronic databases, manually searched citations from relevant articles, and reviewed conference proceedings. The risk of postoperative SSI was pooled using Mantel-Haenszel method.

Results

We identified 18 cohort studies with 16 mainly small studies, addressing the subject. The pooled risk ratio of infection in the HIV patients when compared to non-HIV patients was 1.8 (95% Confidence Interval [CI] 1.3–2.4), in studies in Africa this was 2.3 (95% CI 1.5–3.5). In a sensitivity analysis the risk ratio was reduced to 1.4 (95% CI 0.5–3.8). The risk ratio of infection in patients receiving prolonged antibiotics compared to patients receiving antibiotics for up to 24 hours was 0.7 (95% CI 0.1–4.2).

Conclusions

The results may indicate an increased risk in HIV infected patients but these results are not robust and inconclusive after conducting the sensitivity analysis removing poor quality studies. There is need for larger good quality studies to provide conclusive evidence. To better develop surgical protocols, further studies should determine the effect of reduced CD4 counts, viral load suppression and prolonged antibiotics on the risk for infection.     

Pneumococcal Carriage in Sub-Saharan Africa—A Systematic Review

Background

Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era.

Methods

A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region.

Results

Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6–70.8) in children less than 5 years, 42.6% (95% CI: 29.9–55.4) in children 5–15 years and 28.0% (95% CI: 19.0–37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9–24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes.

Conclusion

Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination.     

Efficacy of Acupuncture for Bell’s Palsy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Acupuncture has emerged as an alternative therapy for Bell’s palsy in both adults and children. However, the use of acupuncture is controversial. We conducted a systematic review and meta-analysis to assess the efficacy of acupuncture for Bell’s palsy. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, irrespective of any language restrictions. Randomized controlled trials comparing acupuncture with other therapies for Bell’s palsy in adults or children were included. Fourteen randomized controlled trials involving 1541 individuals were included in this meta-analysis. Significant association was observed in acupuncture with a higher effective response rate for Bell’s palsy (relative risk, 1.14; 95% confidence interval, 1.04–1.25; P = 0.005) but there was a heterogeneity among the studies (I² = 87%). An assessment of the included studies revealed a high risk of bias in methodological quality. An evaluation of the incidence of complications was not available, owing to incomplete data. Acupuncture seems to be an effective therapy for Bell’s palsy, but there was insufficient evidence to support the efficacy and safety of acupuncture. However, the results should be interpreted cautiously, because of the poor quality and heterogeneity of the included studies.     

Maternal Smoking and the Risk of Cancer in Early Life – A Meta-Analysis

BackgroundIn spite of the well-known harmful effects on the fetus, many women continue smoking during pregnancy. Smoking as an important source of toxic chemicals may contribute to the developmental origin of diseases.ObjectivesThe aim of this work was to pursue the possible association between maternal smoking and cancer in early life. Specifically, we wanted to identify the associated early life cancer types, and to quantify the associations.MethodsIn a systematic literature search 825 articles were identified in PubMed and Web of Science, and 55 more through the reference lists. Of these 62 fulfilled the criteria for inclusion in meta-analyses. Using Mantel-Haenszel or DerSimonian and Laird method, depending on heterogeneity of the studies, pooled estimates and 95% confidence intervals for eight cancer types were calculated.ResultsSmoking during pregnancy was associated with an increased risk for for brain and central nervous system tumors (OR = 1.09; 95% CI = 1.02–1.17). Although the risk for lymphoma was also associated (OR = 1.21; 95% CI = 1.05–1.34), it did not hold up in subgroup analyses. Leukemia was not found to be associated with maternal smoking. Five other cancer types (bone, soft tissue, renal, hepatic, and germ cell cancer) were also examined, but the number of studies was too limited to exclude the possibility of maternal smoking as a risk factor for cancer in offspring.ConclusionsAccording to our meta-analyses, maternal smoking is associated with nervous system cancers, but not with leukemia in early life. Confirming or rejecting associations of maternal smoking with lymphoma and the five other cancer types requires further studies.     

Medical Therapies for Uterine Fibroids – A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials

Background

Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence.

Purpose

To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence.

Study Selection

Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013.

Data Extraction

Two authors independently extracted data from identified studies.

Data Synthesis

A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence—Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated.

Results and Limitations

A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes.

Conclusions

There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed.     

Treatment of Anemia in Inflammatory Bowel Disease– Systematic Review and Meta-Analysis

Background

Anemia is considered the most common systemic complication of inflammatory bowel disease (IBD). We aimed to provide all available evidence regarding the safety and efficacy of therapy existing today to correct anemia in IBD.

Methods

Systematic review and meta-analysis of randomized controlled trials that compared any treatment for anemia in patients with IBD. We searched electronic databases, conference proceedings and clinical trials registries. Two reviewers independently extracted data from included trials. The primary outcome was the effect of treatment for anemia in IBD on the hemoglobin (Hb) response, defined as rate of patients who achieved an increase of 2 g/dl in Hb concentration at the end of the follow-up. Secondary outcomes included disease severity scores, iron indices, Hb levels, inflammatory markers, adverse effects, and mortality. Dichotomous data were analysed by calculating the relative risk (RR) for each trial with the uncertainty in each result being expressed using 95% confidence intervals (CI). A fixed effect model was used, except in the event of significant heterogeneity between the trials (P<0.10, I²>40%), in which we used a random effects model.

Results

Nine trials fulfilled the inclusion criteria, to a total of 973 patients. We were able to perform meta-analysis for intravenous (IV) versus oral iron and for ESAs versus placebo. IV iron was associated with a higher rate of achieving Hb response in comparison to oral iron; RR 1.25 (95% CI 1.04–1.51, I² = 2%, 4 trials), CRP levels and disease activity indexes were not significantly affected by IV iron. IV iron was associated with a decrease in adverse events that required discontinuation of intervention and without an increase in serious adverse.

Discussion

Treatment for anemia in IBD should include IV iron and not oral iron replacement, due to improved Hb response, no added toxicity and no negative effect on disease activity.     

Effect of Diabetes Mellitus Type 2 on Salivary Glucose – A Systematic Review and Meta-Analysis of Observational Studies

Background

Early screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM.

Methods and Findings

We conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge''s g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37).

Conclusions

Our systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients.     

Can Continuous Positive Airway Pressure Reduce the Risk of Stroke in Obstructive Sleep Apnea Patients? A Systematic Review and Meta-Analysis

Background and Purpose

Obstructive sleep apnea (OSA) has been shown to increase the risk of stroke. Although continuous positive airway pressure (CPAP) is considered the treatment of choice for OSA, whether treating OSA with CPAP reduces the risk of stroke remains unclear. We aimed to evaluate the effects of CPAP on incidence of stroke in patients with OSA.

Materials and Methods

We conducted a systematic review and meta-analysis of all published studies that provided the number of incident strokes in OSA patients in light of their treatment status with CPAP.

Results

We identified 8 relevant studies: one randomized controlled study (RCT), 5 cohort studies, and 2 studies using administrative health data. The two overlapping cohort studies in women and the elderly and the 2 studies using administrative health data had analyzed the impact of CPAP on stroke apart from cardiac events, whereas the others had focused on the overall cardiovascular events. Based on a meta-analysis of the cohort studies, treatment with CPAP was associated with a lower incidence of stroke and cardiac events with relative risks of 0.27 [0.14–0.53], and 0.54 [0.38–0.75], respectively, although this could not be reproduced in the RCT and the studies using administrative data.

Conclusions

Treating with CPAP in patients with OSA might decrease the risk of stroke, although there is some conflicting evidence. Such effect was more pronounced in stroke than in cardiac events. Future studies analyzing stroke apart from cardiac disease would be of interest.     

The Prevalence of Disease Clusters in Older Adults with Multiple Chronic Diseases – A Systematic Literature Review

Background

Since most clinical guidelines address single diseases, treatment of patients with multimorbidity, the co-occurrence of multiple (chronic) diseases within one person, can become complicated. Information on highly prevalent combinations of diseases can set the agenda for guideline development on multimorbidity. With this systematic review we aim to describe the prevalence of disease combinations (i.e. disease clusters) in older patients with multimorbidity, as assessed in available studies. In addition, we intend to acquire information that can be supportive in the process of multimorbidity guideline development.

Methods

We searched MEDLINE, Embase and the Cochrane Library for all types of studies published between January 2000 and September 2012. We included empirical studies focused on multimorbidity or comorbidity that reported prevalence rates of combinations of two or more diseases.

Results

Our search yielded 3070 potentially eligible articles, of which 19 articles, representing 23 observational studies, turned out to meet all our quality and inclusion criteria after full text review. These studies provided prevalence rates of 165 combinations of two diseases (i.e. disease pairs). Twenty disease pairs, concerning 12 different diseases, were described in at least 3 studies. Depression was found to be the disease that was most commonly clustered, and was paired with 8 different diseases, in the available studies. Hypertension and diabetes mellitus were found to be the second most clustered diseases, both with 6 different diseases. Prevalence rates for each disease combination varied considerably per study, but were highest for the pairs that included hypertension, coronary artery disease, and diabetes mellitus.

Conclusions

Twenty disease pairs were assessed most frequently in patients with multimorbidity. These disease combinations could serve as a first priority setting towards the development of multimorbidity guidelines, starting with the diseases with the highest observed prevalence rates and those with potential interacting treatment plans.     

The Tip of the “Celiac Iceberg” in China: A Systematic Review and Meta-Analysis

Objective

Until recently, celiac disease was considered to be rare in China. We aimed to estimate its true status.

Methods

By searching the MEDLINE database and four Chinese full-text databases (CNKI, CBM, VIP and WANFANG) (up to August 2012), as well as two HLA allele frequency net databases and the Chinese Statistics Yearbook databases, we systematically reviewed the literature on definite and suspected cases of celiac disease, the predisposing HLA allele frequencies, and on gluten exposure in China. Meta-analysis was performed by analyzing DQ2, DQ8 and DQB1*0201 gene frequencies and heterogeneity in populations from different geographic regions and ethnicities in China.

Results

At present, the number of reported celiac disease cases is extremely low in China. The frequencies of the HLA-DQ2.5 and HLA-DQ8 haplotypes were 3.4% (95% confidence interval 1.3–5.5%) and 2.1% (0.1–4.1%), respectively. HLA-DQ2 and HLA-DQ8 antigen frequencies were 18.4% (15.0–21.7%) and 8.0% (4.5–11.4%), respectively. The frequency of the DQB1*0201 allele was 10.5% (9.3–11.6%) and it was more common in the northern Chinese than in the southern Chinese populations. The chance of being exposed to gluten is rapidly increasing all over China nowadays.

Conclusion

The data on HLA haplotyping, in conjunction with increasing wheat consumption, strongly suggests that the occurrence of celiac disease is more common in China than currently reported. Coordinated measures by the Chinese government, medical and agricultural research institutions, and food industries, would be justified to create more awareness about celiac disease and to prevent it becoming a medical and societal burden.     

Does the Chemotherapy Backbone Impact on the Efficacy of Targeted Agents in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis of the Literature

ImportanceThe EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC.ObjectiveTo document the overall impact of specific chemotherapy regimens on the efficacy of targeted agents in treating patients with mCRC. Data sources: MEDLINE, EMBASE and Cochrane databases were searched to 2014, supplemented by hand-searching ASCO/ESMO conference abstracts.ResultsEGFR-I added to irinotecan-based chemotherapy modestly improved OS with HR 0.90 (95% CI 0.81–1.00, p = 0.04), but more so PFS with HR 0.77 (95% CI 0.69–0.86, p<0.00001). No benefit was evident for EGFR-I added to oxaliplatin-based chemotherapy (OS HR 0.97 (95% CI 0.87–1.09) and PFS HR 0.92 (95% CI 0.83–1.02)). Significant oxaliplatin-irinotecan subgroup interactions were present for PFS with I² = 82%, p = 0.02. Further analyses of oxaliplatin+EGFR-I trials showed greater efficacy with infusional 5FU regimens (PFS HR 0.82, 95% CI 0.72–0.94) compared to capecitabine (HR 1.09; 95% CI 0.91–1.30) and bolus 5FU (HR 1.07; 95% CI 0.79–1.45); subgroup interaction was present with I² = 72%, p = 0.03. The oxaliplatin-irinotecan interaction was not evident for infusional 5FU regimens. For AIs, OS benefit was observed with both oxaliplatin-based (HR 0.83) and irinotecan-based (HR 0.77) regimens without significant subgroup interactions. Oxaliplatin+AI trials showed no subgroup interactions by type of FP, whilst an interaction was present for irinotecan+AI trials although aflibercept was only used with infusional FP (I² = 89.7%, p = 0.002).

Conclusion and Relevance

The addition of EGFR-I to irinotecan-based chemotherapy has consistent efficacy, regardless of FP regimen, whereas EGFR-I and oxaliplatin-based regimens were most active with infusional 5FU. No such differential activity was observed with the varying chemotherapy schedules when combined with AIs.     

Rotigotine Transdermal Patch in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Background and Methods

The efficacy and safety of rotigotine transdermal patch in Parkinson’s disease (PD) were studied in some clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy, tolerability, and safety of rotigotine transdermal patch versus placebo in PD.

Results

Six randomized controlled trials (1789 patients) were included in this meta-analysis. As compared with placebo, the use of rotigotine resulted in greater improvements in Unified Parkinson’s Disease Rating Scale activities of daily living score (weighted mean difference [WMD] –1.69, 95% confidence interval [CI] –2.18 to –1.19), motor score (WMD –3.86, 95% CI –4.86 to –2.86), and the activities of daily living and motor subtotal score (WMD –4.52, 95% CI –5.86 to –3.17). Rotigotine was associated with a significantly higher rate of withdrawals due to adverse events (relative risk [RR] 1.82, 95% CI 1.29–2.59), and higher rates of application site reactions (RR 2.92, 95% CI 2.29–3.72), vomiting (RR 5.18, 95% CI 2.25–11.93), and dyskinesia (RR 2.52, 95% CI 1.47–4.32) compared with placebo. No differences were found in the relative risks of headache, constipation, back pain, diarrhea, or serious adverse events.

Conclusions

Our meta-analysis showed that the use of rotigotine can reduce the symptoms of PD. However, rotigotine was also associated with a higher incidence of adverse events, especially application site reactions, compared with placebo.     

Can Falls Risk Prediction Tools Correctly Identify Fall-Prone Elderly Rehabilitation Inpatients? A Systematic Review and Meta-Analysis

Background

Falls of elderly people may cause permanent disability or death. Particularly susceptible are elderly patients in rehabilitation hospitals. We systematically reviewed the literature to identify falls prediction tools available for assessing elderly inpatients in rehabilitation hospitals.

Methods and Findings

We searched six electronic databases using comprehensive search strategies developed for each database. Estimates of sensitivity and specificity were plotted in ROC space graphs and pooled across studies. Our search identified three studies which assessed the prediction properties of falls prediction tools in a total of 754 elderly inpatients in rehabilitation hospitals. Only the STRATIFY tool was assessed in all three studies; the other identified tools (PJC-FRAT and DOWNTON) were assessed by a single study. For a STRATIFY cut-score of two, pooled sensitivity was 73% (95%CI 63 to 81%) and pooled specificity was 42% (95%CI 34 to 51%). An indirect comparison of the tools across studies indicated that the DOWNTON tool has the highest sensitivity (92%), while the PJC-FRAT offers the best balance between sensitivity and specificity (73% and 75%, respectively). All studies presented major methodological limitations.

Conclusions

We did not identify any tool which had an optimal balance between sensitivity and specificity, or which were clearly better than a simple clinical judgment of risk of falling. The limited number of identified studies with major methodological limitations impairs sound conclusions on the usefulness of falls risk prediction tools in geriatric rehabilitation hospitals.     

Using Multiple Types of Studies in Systematic Reviews of Health Care Interventions – A Systematic Review

Background

A systematic review may evaluate different aspects of a health care intervention. To accommodate the evaluation of various research questions, the inclusion of more than one study design may be necessary. One aim of this study is to find and describe articles on methodological issues concerning the incorporation of multiple types of study designs in systematic reviews on health care interventions. Another aim is to evaluate methods studies that have assessed whether reported effects differ by study types.

Methods and Findings

We searched PubMed, the Cochrane Database of Systematic Reviews, and the Cochrane Methodology Register on 31 March 2012 and identified 42 articles that reported on the integration of single or multiple study designs in systematic reviews. We summarized the contents of the articles qualitatively and assessed theoretical and empirical evidence. We found that many examples of reviews incorporating multiple types of studies exist and that every study design can serve a specific purpose. The clinical questions of a systematic review determine the types of design that are necessary or sufficient to provide the best possible answers. In a second independent search, we identified 49 studies, 31 systematic reviews and 18 trials that compared the effect sizes between randomized and nonrandomized controlled trials, which were statistically different in 35%, and not different in 53%. Twelve percent of studies reported both, different and non-different effect sizes.

Conclusions

Different study designs addressing the same question yielded varying results, with differences in about half of all examples. The risk of presenting uncertain results without knowing for sure the direction and magnitude of the effect holds true for both nonrandomized and randomized controlled trials. The integration of multiple study designs in systematic reviews is required if patients should be informed on the many facets of patient relevant issues of health care interventions.     

Persistent Difficulties in Switching to Second-Line ART in Sub-Saharan Africa — A Systematic Review and Meta-Analysis

Objectives

Switching to second-line antiretroviral therapy (ART) largely depends on careful clinical assessment and access to biological measurements. We performed a systematic review and meta-analysis to estimate the incidence of switching to second-line ART in sub-Saharan Africa and its main programmatic determinants.

Methods

We searched 2 databases for studies reporting the incidence rate of switching to second-line ART in adults living in sub-Saharan Africa. Data on the incidence rate of switching were pooled, and random-effect models were used to evaluate the effect of factors measured at the programme level on this incidence rate.

Results

Nine studies (157,340 patients) in 21 countries were included in the meta-analysis. All studies considered patients under first-line ART and conditions to initiate ART were similar across studies. Overall, 3,736 (2.4%) patients switched to second-line ART. Incidence rate of switch was in mean 2.65 per 100 person-years (PY) (95% confidence interval: 2.01–3.30); it ranged from 0.42 to 4.88 per 100 PY and from 0 to 4.80 per 100 PY in programmes with and without viral load monitoring, respectively. No factors measured at the programme level were associated with the incidence rate of switching to second-line ART.

Conclusion

The low incidence rate of switching to second-line ART suggests that the monitoring of patients under ART is challenging and that access to second-line ART is ineffective; efforts should be made to increase access to second-line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen.     

The Association between Near Work Activities and Myopia in Children—A Systematic Review and Meta-Analysis

Myopia has a multifactorial etiology, although environmental factors are predominant in determining its current patterns. Currently, associations between near work activities and myopia have not been consistently observed. Therefore, we performed a systematic review to quantify the effect of near work activities on myopia in children. Relevant articles published between 1989 and 2014 were identified in MEDLINE, Embase, and the Cochrane Library, and the citation lists were reviewed. Twelve cohort studies and 15 cross-sectional studies were included (25,025 children aged between 6 and 18 years). The I² statistic was used to assess heterogeneity. Study-level data were pooled using a random-effects model or a fixed-effects model (when less than 5 studies were included). We found that more time spent on near work activities was associated with higher odds of myopia (odds ratio [OR] = 1.14; 95% confidence interval [CI] = 1.08–1.20) and that the odds of myopia increased by 2% (OR:1.02; 95% CI = 1.01–1.03) for every one diopter-hour (hr) more of near work per week. Therefore, the development of a strategy to reduce the impact of near work on myopia would be important for preventing myopia in children.     

Changes in Olfactory Bulb Volume in Parkinson’s Disease: A Systematic Review and Meta-Analysis

Objective

The changes in olfactory bulb (OB) volume in Parkinson’s disease (PD) patients have not yet been comprehensively evaluated. The purpose of this meta-analysis was to explore whether the OB volume was significantly different between PD patients and healthy controls.

Methods

PubMed and Embase were searched up to March 6, 2015 with no language restrictions. Two independent reviewers screened eligible studies and extracted data on study characteristics and OB volume. Additionally, a systematic review and meta-analysis using a random-effects model were conducted. Publication bias was determined by using funnel plots and Begg’s and Egger’s tests. Subgroup analyses were performed to assess possible sources of heterogeneity.

Results

Six original case-control studies of 216 PD patients and 175 healthy controls were analyzed. The pooled weighted mean difference (WMD) in the OB volume between the PD patients and the healthy participants was -8.071 for the right OB and -10.124 for the left OB; these values indicated a significant difference among PD patients compared with healthy controls. In addition, a significant difference in the lateralized OB volume was observed in PD patients, with a pooled WMD of 1.618; these results indicated a larger right OB volume than left OB volume in PD patients. In contrast, no difference in the lateralized OB volume was found in healthy controls. No statistical evidence of publication bias among studies was found based on Egger’s or Begg’s tests. Sensitivity analyses revealed that the results were consistent and robust.

Conclusions

Overall, both the left and the right OB volume were significantly smaller in PD patients than in healthy controls. However, significant heterogeneity and an insufficient number of studies underscore the need for further observational research.