Aromatherapy for stress reduction in healthy adults: a systematic review and meta-analysis of randomized clinical trials

The aim of this review was to systematically assess the effectiveness of aromatherapy for stress management. Seven databases were searched from their inception through April 2014. RCTs testing aromatherapy against any type of controls in healthy human person that assessed stress level and cortisol level were considered. Two reviewers independently performed the selection of the studies, data abstraction and validations. The risk of bias was assessed using Cochrane criteria. Five RCTs met our inclusion criteria, and most of them had high risk of bias. Four RCTs tested the effects of aroma inhalation compared with no treatment, no aroma, and no odour oil. The meta-analysis suggested that aroma inhalation has favourable effects on stress management (n = 80; standard mean difference (SMD), −0.96; 95% CI, −1.44 to −0.48; P < 0.0001; I² = 0%). Three of included RCTs tested aroma inhalation on saliva or serum cortisol level compared with control and meta-analysis failed to show significant difference between two groups (n = 88, SMDs −0.62; 95% CIs −1.26 to 0.02, P = 0.06, I² = 46%). In conclusion, there is limited evidence suggesting that aroma inhalation may be effective in controlling stress. However, the number, size and quality of the RCTs are too low to draw firm conclusions.     

Exercise training for managing behavioral and psychological symptoms in people with dementia: A systematic review and meta-analysis

This systematic review and meta-analysis of randomized controlled trials assessed the effects of exercise on behavioral and psychological symptoms of dementia (BPSD, including depression) in people with dementia (PWD). Secondary outcomes for the effects of exercise were mortality and antipsychotic use. Twenty studies were included in this review (n = 18 in the meta-analysis). Most studies used a multicomponent exercise training (n = 13) as intervention; the control group was often a usual care (n = 10) or a socially-active (n = 8) group. Exercise did not reduce global levels of BPSD (n = 4. Weighted mean difference −3.884; 95% CI −8.969–1.201; I² = 69.4%). Exercise significantly reduced depression levels in PWD (n = 7). Standardized mean difference −0.306; 95% CI −0.571 to −0.041; I² = 46.8%); similar patterns were obtained in sensitivity analysis performed among studies with: institutionalized people (p = 0.038), multicomponent training (p = 0.056), social control group (p = 0.08), and low risk of attrition bias (p = 0.11). Exploratory analysis showed that the principal BPSD (other than depression) positively affected by exercise was aberrant motor behavior. Exercise had no effect on mortality. Data on antipsychotics were scarce. In conclusion, exercise reduces depression levels in PWD. Future studies should examine whether exercise reduces the use (and doses) of antipsychotics and other drugs often used to manage BPSD.     

Nerve-sparing radical hysterectomy versus conventional radical hysterectomy in early-stage cervical cancer. A systematic review and meta-analysis of survival and quality of life

Background and aimsSurvival after radical hysterectomy (RH) for early-stage cervical cancer is good. Hence quality of life (QOL) after treatment is an important issue. Nerve-sparing radical hysterectomy (NSRH) improves QOL by selectively sparing innervation of bladder, bowel and vagina, reducing therapy-induced morbidity. However, the oncological outcome and the functional outcome after NSRH are subjects of debate. We aim to present the best possible evidence available regarding both QOL and survival after NSRH in early-stage cervical cancer.MethodsSystematic review and meta-analysis on studies comparing NSRH and RH.ResultsForty-one studies were included, and 27 were used for the meta-analysis. There was no difference in 2-, 3- and 5-year overall survival: the risk ratios (RRs) were respectively 1.02 (95% CI 0.99–1.05, n = 879), 1.01 (95% CI 0.95–1.08, n = 1324) and 1.03 (95% CI 0.99–1.08, n = 638). No difference was found in 2-, 3- and 5-year disease-free survival: RR 1.01 (95% CI 0.95–1.05, n = 1175), 0.99 (95% CI 0.94–1.03, n = 1130) and 1.00 (95% CI 0.95–1.06, n = 933) respectively. Post-operative time to micturition was significantly shorter in the NSRH group: standardized mean difference (SMD) −0.84 (CI 95% −1.07 to −0.60).ConclusionsNSRH can be considered safe and effective for early-stage cervical cancer since short- and long-term survival do not differ from those of conventional RH, while bladder function after NSRH is significantly less impaired.     

Social networks for improving healthy weight loss behaviors for overweight and obese adults: A randomized clinical trial of the social pounds off digitally (Social POD) mobile app

ObjectiveTo test the efficacy of a weight loss mobile app based on recommender systems and developed by experts in health promotion and computer science to target social support and self-monitoring of diet, physical activity (PA), and weight (Social POD app), compared to a commercially available diet and PA tracking app (standard).Materials and methodsOverweight adults [N = 51] were recruited and randomly assigned to either the experimental group [n = 26; theory-based podcasts (TBP) + Social POD app] or the comparison group (n = 25; TBP + standard app). The Social POD app issued notifications to encourage users to self-monitor and send theory-based messages to support users who had not self-monitored in the previous 48 h. Independent samples t-test were used to examine group differences in kilograms lost and change in BMI. Analysis of covariance was used to analyze secondary outcomes while controlling for baseline values.ResultsParticipant attrition was 12% (n = 3 experimental and n = 3 comparison). Experimental group participants lost significantly more weight (−5.3 kg, CI: −7.5, −3.0) than comparison group (−2.23 kg, CI: −3.6, −1.0; d = 0.8, r = 0.4, p = 0.02) and had a greater reduction in BMI (p = 0.02). While there were significant differences in positive outcome expectations between groups (p = 0.04) other secondary outcomes (e.g., caloric intake and social support) were not significant.DiscussionUse of the Social POD app resulted in significantly greater weight loss than use of a commercially available tracking app. This mobile health intervention has the potential to be widely disseminated to reduce the risk of chronic disease associated with overweight and obesity.     

The impact of medical informatics on patient satisfaction: A USA-based literature review

PurposePatient satisfaction is increasingly recognized as an important component of quality. The expansion of health information technologies (HIT) might have an impact on patient satisfaction – either positively or negatively. We conducted a literature review to explore the impact of these technologies on patient satisfaction.MethodsThe database of PubMed was searched from inception through May 2010, using the MeSH terms “Medical Informatics” and “Patient Satisfaction”. We included all original interventional studies regardless of their study design that were published in English and were evaluating HIT impact on patient satisfaction. Studies were categorized by technology type according to the American Medical Informatics Association framework and by study design. The major outcome of interest was the HIT impact on patient satisfaction.ResultsOf 1293 citations reviewed, 56 studies met our inclusion criteria. Design of these studies included mostly randomized controlled trials (RCTs) (n = 20, 36%), cross-sectional surveys (n = 17, 30%), and a pre and post studies (n = 14, 25%). Overall, 54% (n = 30) of the studies demonstrated a positive effect of HIT on patient satisfaction, 34% (n = 19) failed to show any effect, 11% (n = 6) had inconclusive results, and 2% (n = 1) revealed a negative effect. Of the 20 RCTs, 40% (n = 8) showed a positive effect of HIT on patient satisfaction, 50% (n = 10) failed to show any effect, and 10% (2) had inconclusive results.ConclusionsAnalysis suggested that while there is some evidence that HIT improves patient satisfaction, studies in this literature review, and in particularly RCTs, were not consistent in their findings. Although HIT may be a promising tool to improve patient satisfaction, more well-designed research studies are needed in order to get a better understanding of this domain and accordingly find new opportunities to improve quality of care.     

KIR alloreactivity based on the receptor–ligand model is associated with improved clinical outcomes of allogeneic hematopoietic stem cell transplantation: Result of single center prospective study

Receptors on natural killer (NK) cells, named killer immunoglobulin-like receptors (KIRs), recognize HLA class I alleles. Patients (n = 59) who received allogeneic hematopoietic stem cell transplantation (HSCT) from either a related (n = 17) or unrelated donor (n = 42) in Samsung Medical Center (Seoul, South Korea) were included. KIR mismatch was defined as incompatibility between the donor KIR and recipient KIR ligand (receptor–ligand model), and all cases were classified into the two broad haplotypes of KIR A and B. Patients with acute leukemia (n = 51, 86.4%) or myelodysplastic syndrome (n = 8, 13.6%) were included. Peripheral blood was used as the source of stem cells in all patients. Kaplan–Meier survival curves for overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) favored recipients with a KIR-mismatched donor, although the differences were not statistically significant. In multivariate analysis, KIR mismatch was an independent prognostic indicator of a better OS (P = 0.010, HR = 0.148, 95% CI 0.034–0.639), DFS (P = 0.022, HR = 0.237, 95% CI 0.069–0.815), and CIR (P = 0.031, HR = 0.117, 95% CI 0.017–0.823). OS, DFS, and CIR did not differ significantly between the KIR A and B haplotypes.     

Comparison the effect of lateral wedge insole and acupuncture in medial compartment knee osteoarthritis: A randomized controlled trial

BackgroundThere is lack of well-designed trials evaluating structural benefits of non-pharmacologic therapies in knee osteoarthritis (OA). In this parallel-group randomized controlled trial, we aim to compare the possible advantages of lateral wedge insole and acupuncture in patients with medial knee OA.MethodPatients with grade two or three of medial knee OA were randomly allocated to group one who received an in shoe lateral wedge and group two who underwent acupuncture. We assessed patients' pain, function and knee joint cartilage thickness before and after intervention. Paired t-test and independent samples t-test were used for in group and between group analyses. (Level of evidence: 2.)ResultsTwenty patients in each group were recruited in the study. Pain significantly decreased after therapy in both groups one and two (paired t test, P < 0.001, 95% CI: 1.62–3.25 and 1.58–3.20 respectively). Function improved in each group (paired t test, P = 0.001, 95% CI of 0.94–2.38 in group one and 0.97–2.43 in group two). A non-clinically statistically significant difference regarding the femoral and tibial cartilage thickness was obtained in both groups one (P = 0.005, CI: − 0.43–0.82 and P = 0.037, CI: − 0.44–0.80 respectively) and two (P = 0.025, CI: − 0.45–0.79 and P = 0.035, CI: − 0.29–0.96 respectively). Between groups analysis showed no significant difference regarding abovementioned measures.ConclusionBoth lateral wedge insole and acupuncture can be effective in the treatment of medial knee osteoarthritis without any superiority of one over the other.Iranian Registry of Clinical Trials: IRCT201201108235N1.URL: http://irct.ir/searchen.php     

Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: A randomized controlled trial

ObjectiveTo evaluate the effects of escitalopram 10–20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes.Study designA double-blind, placebo-controlled randomized trial of escitalopram 10–20 mg/day vs. identical placebo was conducted among 205 women ages 40–62 years with an average of ≥4 daily hot flashes recruited at 4 clinical sites from July 2009 to June 2010.Main outcome measuresThe primary trial outcomes, reported previously, were the frequency and severity of vasomotor symptoms at 8 weeks. Here, we report on the pre-specified secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and the pain intensity and interference scale (PEG).ResultsOutcome data were collected on 97% of randomized women and 87% of women took at least 70% of their study medication. Treatment with escitalopram resulted in significantly greater improvement in total MENQOL scores (mean difference at 8 weeks of −0.41; 95% confidence interval (CI) −0.71 to −0.11; p < 0.001), as well as Vasomotor, Psychosocial, and Physical domain scores with the largest difference seen in the Vasomotor domain (mean difference −0.75; 95% CI −1.28 to −0.22; p = 0.02). There was no significant treatment group difference for the Sexual Function domain. Escitalopram treatment resulted in statistically significant improvements in PEG scores compared to placebo (mean treatment group difference at 8 weeks of −0.33; 95% CI −0.81 to 0.15; p = 0.045).ConclusionsTreatment with escitalopram 10–20 mg/day in healthy women with vasomotor symptoms significantly improved menopause-related quality of life and pain.     

Efficacy of different antifungal drugs as initial treatment for patients with talaromycosis: A systematic review and meta-analysis

There are no standard choices on antifungal drugs for talaromycosis due to various factors, and related studies are also limited. This study summarizes and analyzes efficacy of different antifungal drugs for patients with talaromycosis, which can provide more reference evidence for drugs’ choices in practice. We conducted a meta-analysis on prognostic impacts of different antifungal drugs against talaromycosis, and primary outcome was all-cause mortality. A total of 975 patients from 8 studies were included. One of the 8 studies was a randomized controlled trial and the others were retrospective studies. Among these patients, 582 cases were initiated with amphotericin B, 31 cases died (9.28%). The other 393 cases were initiated with itraconazole, and 54 cases died (14.00%). The initial use of amphotericin B for talaromycosis significantly reduced mortality compared with itraconazole (risk ratio (RR): 0.61; 95% confidence interval (CI): 0.41–0.90; P = 0.01; I² = 4%). Initial treatment with amphotericin B for talaromycosis in different regions (internal and external) and studies (sample size < 100) had no obvious prognostic advantages over itraconazole (RR: 0.60, 95% CI: 0.32–1.13; P = 0.11; I² = 44%; RR: 0.61, 95% CI: 0.37– 1.00; P = 0.05; I² = 0%; RR: 0.71, 95% CI: 0.39–1.29; P = 0.26; I² = 0%, respectively). However, when study's sample size was ≥ 100, the mortality of amphotericin B group was significantly reduced (RR: 0.54, 95% CI: 0.32– 0.92; P = 0.02; I² = 46%). In conclusion, amphotericin B is a better choice as initial therapeutic drug for talaromycosis.     

Mobile bearing or fixed bearing? A meta-analysis of outcomes comparing mobile bearing and fixed bearing bilateral total knee replacements

BackgroundTo compare outcomes between mobile-bearing (MB) and fixed-bearing (FB) in bilateral total knee replacements.MethodsThe MEDLINE, EMBASE and Cochrane Library databases were searched. Randomized controlled trials of bilateral total knee arthroplasty with one of each design implanted were identified. Weighted mean differences (WMDs) and pooled risk ratios (RRs) were calculated using fixed- or random-effects models.ResultsTwelve studies were identified with a total of 807 patients and 1614 knees. All RCTs were of high quality with a low risk of bias. No statistical difference was found between MB and FB at 2- to 5-year follow-up in terms of America Knee Society score (WMD: − 1.29, 95% CI: − 5.65 to 3.06), pain score (WMD: − 3.26, 95% CI: − 10.45 to 3.93), range of motion (WMD: − 4.16, 95% CI: − 9.97 to 1.66), reoperation (RR: 1.00, 95% CI: 0.28 to 3.60), and radiolucent lines (RR: 1.51, 95% CI: 0.70 to 3.24). The results were similar at 1-, 5- to 8-, or > 8-year follow-up. Patient's satisfaction (RR: 0.85, 95% CI: 0.54 to 1.34), and complication (≤ 2-year, RR: 0.55, 95% CI: 0.29 to 1.04; > 2-year, RR: 1.0, 95% CI = 0.73 to 1.38) also showed no difference between two groups.ConclusionsBased on this meta-analysis we are unable to detect the superiority of MB as compared to FB. More randomized trials with a larger sample size and longer follow-up are needed to evaluate these two kinds of prosthesis.Level of evidenceTherapeutic Level II.     

Dengue virus infection during pregnancy increased the risk of adverse fetal outcomes? An updated meta-analysis

ObjectiveTo evaluate the effect of maternal dengue virus (DENV) infection during pregnancy in premature birth, low birth weight, miscarriage and stillbirth.MethodsSystematic electronic literature searches were conducted including PubMed, Medline, Embase, Web of science, Scopus and the Cochrane Library database, up until July 5, 2017. Effect sizes were estimated by using the relative risk (RR) or odds ratio (OR) with theirs corresponding 95% confidence interval (CI). Subgroup analyses were conducted for study design (prospective or retrospective) and clinical symptom of participants (symptomatic or asymptomatic). Statistical analysis was conducted by STATA 12.0.ResultsThe initial systematic literature searches identified 1048 studies. After screening, fourteen studies were included. The pooled results did not suggest maternal DENV infection might increase the risk of adverse fetal outcomes with a pooled RR of 0.96 (95% CI: 0.85–1.09, I² = 49.6%) for premature birth, RR of 0.99 (95%CI: 0.87–1.12, I² = 35.1%) for low birth weight, OR of 1.77 (95% CI: 0.99–3.15, I² = 17.5%) for miscarriage and RR of 3.42 (95% CI: 0.76–15.49, I² = 54.8%) for stillbirth. Subgroup analysis of studies in symptomatic participants still did not indicate DENV infection appeared to be a risk factor for premature birth, low birth weight and miscarriage with pooled effect size of 0.99 (95% CI: 0.87–1.13, I² = 49.3%), 1.22 (95% CI: 0.827–1.80, I² = 55.1%) and 1.19 (95% CI: 0.56–2.55, I² = 4.7%), respectively.ConclusionsCurrent evidence did not suggest that maternal DENV infection during pregnancy might increase the risk of premature birth, low birth weight, miscarriage and stillbirth.     

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

PurposeWe assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.MethodsRetrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.ResultsThe ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25–1.33], P = 3×10⁻⁷²). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27–1.36], P = 7×10⁻⁵⁰). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25–1.40], P = 3×10⁻²²) and BRCA2 (HR = 1.44 [95% CI 1.30–1.60], P = 4×10⁻¹²) carriers. The associations in the prospective cohort were similar.ConclusionPopulation-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Démarche diagnostique en auto-immunité : apport de la technologie Multiplex. Exemple de la gamme QUANTA Plex™ (Inova)

The detection of autoantibodies was often useful to diagnose and/or to classify autoimmune diseases.ObjectiveThe aim of this study was to compare the new Luminex^™ technology for anti-ENA, ANCA, anti-TPO and anti-TG antibodies detection with conventional methods.MethodsQUANTA Plex^™ SLE 8, ANCA and Thyroid Profile provided by Inova (Ménarini, France) were used to analyze 815 serum samples sent to the laboratory for the detection of anti-ENA (n = 400), ANCA (n = 161), anti-thyroid antibodies (n = 254).ResultsFor anti-ENA detection, the global concordance was 95.6%. For ANCA detection, the concordance was respectively 78.5 and 91.4% for anti-PR3 and anti-MPO. For thyroid antibodies, the concordance was respectively 90 and 88% for anti-TPO and anti-TG.ConclusionUse of QUANTA Plex^™ Profiles was easy to rapidly and simultaneously detect the most common autoantibodies in autoimmune diseases. These tests appear to be specific and sensitive and will be promute in diagnosis of autoimmune diseases.     

Ultrastructural examination of skin biopsies may assist in diagnosing mitochondrial cytopathy when muscle biopsies yield negative results

Ultrastructural evaluation of skin biopsies has been utilized for diagnosis of mitochondrial disease. This study investigates how frequently skin biopsies reveal mitochondrial abnormalities, correlates skin and muscle biopsy findings, and describes clinical diagnoses rendered following the evaluation. A retrospective review of surgical pathology reports from 1990 to 2015 identified skin biopsies examined by electron microscopy for suspected metabolic disease. A total of 630 biopsies were included from 615 patients. Of these patients, 178 also underwent a muscle biopsy. Of the 630 skin biopsies, 75 (12%) showed ultrastructural abnormalities and 34 (5%) specifically showed mitochondrial abnormalities including increased size (n = 27), reduced or abnormal cristae (n = 23), dense matrices (n = 20), and increased number (n = 8). Additional findings included lysosomal abnormalities (n = 13), lipid accumulation (n = 2) or glycogen accumulation (n = 1). Of the 34 patients with mitochondrial abnormalities on skin biopsy, 20 also had muscle biopsies performed and nine showed abnormalities suggestive of a mitochondrial disorder including absent cytochrome oxidase staining (n = 2), increased subsarcolemmal NADH, SDH, or cytochrome oxidase staining (n = 1), or ultrastructural findings including large mitochondrial size (n = 5), abnormal mitochondrial structure (n = 5), and increased mitochondrial number (n = 4). The most common presenting symptoms were intellectual disability (n = 13), seizures (n = 12), encephalopathy (n = 9), and gastrointestinal disturbances (n = 9). At last known follow-up, 12 patients had a definitive diagnosis of a mitochondrial disorder. One patient each had Complex I deficiency, Complex III deficiency, Charcot-Marie-Tooth disease, pyruvate dehydrogenase deficiency, and Phelan-McDermid syndrome. Our results suggest that skin biopsy sometimes yields diagnostic clues suggestive of a mitochondrial cytopathy in cases with a negative muscle biopsy.     

Human papillomavirus is detectable in Barrett's esophagus and esophageal carcinoma but is unlikely to be of any etiologic significance

Barrett's esophagus (BE), a known precursor of esophageal adenocarcinoma has recently been associated with human papillomavirus (HPV). p16^INK4a expression is a recognized surrogate marker of HPV infection in the cervix.ObjectivesThis study has assessed the possible role of human papillomavirus (HPV) infection in BE and esophageal adenocarcinoma, in the North American population by screening esophageal tissues for HPV by a combination of assays.Study designFormalin-fixed, paraffin-embedded blocks from cases of Barrett's esophagus (n = 84), esophageal adenocarcinoma (n = 36) and normal gastro-esophageal junction (n = 29) were examined for HPV by PCR, chromogenic in situ hybridization, and p16^INK4a immunohistochemistry.ResultsHPV DNA was detected by PCR in 23 of 84 (27.4%) BE cases, 11 of 36 (31%) cases of adenocarcinoma and in 7 of 29 (24%) normal control cases (p = 0.82). p16^INK4a staining was positive in 10 (12%) cases of BE, 15 (42%) cases of adenocarcinoma and 6 (21%) cases of the control group. Positive p16^INK4a staining was not statistically different between the three groups whether positive or negative for HPV DNA (p = 0.91 and p = 0.91 respectively). Similarly, negative p16^INK4a staining did not show a difference between the three groups for whether positive or negative for HPV DNA (p = 0.50 and p = 0.28, respectively). HPV was not detected by CISH in the adenocarcinomas while in BE and control groups, CISH was non-contributory.ConclusionsThese data suggest that while HPV is detectable in a subset of esophageal lesions and tumors, the HPV detected is unlikely to be of etiologic significance or a factor accounting for the increase in BE and esophageal adenocarcinoma cases in the United States.     

Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized,multicenter, double-blind clinical trial and extension study

PurposeOutcomes in patients with Fabry disease receiving migalastat during the phase 3 FACETS trial (NCT00925301) were evaluated by phenotype.MethodsData were evaluated in two subgroups of patients with migalastat-amenable GLA variants: “classic phenotype” (n = 14; males with residual peripheral blood mononuclear cell α-galactosidase A <3% normal and multiorgan system involvement) and “other patients” (n = 36; males not meeting classic phenotype criteria and all females). Endpoints included estimated glomerular filtration rate (eGFR), left ventricular mass index (LVMi), Gastrointestinal Symptoms Rating Scale diarrhea subscale (GSRS-D), renal peritubular capillary (PTC) globotriaosylceramide (GL-3) inclusions, and plasma globotriaosylsphingosine (lyso-Gb₃).ResultsBaseline measures in the classic phenotype patients suggested a more severe phenotype. At month 24, mean (SD) annualized change in eGFR_CKD-EPI with migalastat was −0.3 (3.76) mL/min/1.73 m² in the classic phenotype subgroup; changes in LVMi, GSRS-D, and lyso-Gb₃ were −16.7 (18.64) g/m², −0.9 (1.66), and −36.8 (35.78) nmol/L, respectively. At month 6, mean PTC GL-3 inclusions decreased with migalastat (−0.8) and increased with placebo (0.3); switching from placebo to migalastat, PTC inclusions decreased by −0.7. Numerically smaller changes in these endpoints were observed in the other patients.ConclusionMigalastat provided clinical benefit to patients with Fabry disease and amenable variants, regardless of disease severity.     

A systematic review and meta-analysis of the impact of oral nutritional supplements on hospital readmissions

The adverse effects of disease-related malnutrition (DRM) on health care use and costs are well substantiated. However, the impact of managing DRM with nutritional support on health care use, including hospital (re)admissions requires exploration. This systematic review (9 RCT, N = 1190) examined the effects of oral nutritional supplements (ONS) on hospital (re)admissions. Meta-analysis of 6 RCT (N = 852) with data on the proportion of patients (re)admitted to hospital showed significant reductions with ONS vs. routine care (OR 0.59, 95% CI 0.43–0.80, P = 0.001), including 5 RCT (N = 826) that recorded readmissions (OR 0.59, 95% CI 0.43–0.80, P = 0.001). The significant reduction in (re)admissions was found in meta-analyses of ONS trials in various settings and in patients with DRM or of varied nutritional status. A larger meta-analysis (8 RCT, N = 999) that combined other (re)admissions data using standardised differences also showed a significant reduction with ONS (effect size ?0.23, 95% CI ?0.36 to ?0.10, P = 0.001). Most of these trials (75%) were in older people aged ≥65 years (6 RCT, N = 834, effect size ?0.18, 95% CI ?0.31 to ?0.04, P = 0.011). This systematic review shows that ONS significantly reduce hospital (re)admissions, particularly in older patient groups, with economic implications for health care.     

Insulin growth factor (IGF) 1, IGF-binding proteins and ovarian cancer risk: A systematic review and meta-analysis

BackgroundInsulin resistance (IR) has been implicated in carcinogenesis, but there is no consensus regarding its involvement in ovarian cancer. We performed a systematic review and meta-analysis to evaluate the association between IR and ovarian cancer.MethodsSearches were conducted in five databases for studies evaluating IR markers (levels of serum insulin, C peptide, insulin growth factor [IGF] 1 and IGF-binding proteins [IGFBPs], homeostatic model assessment insulin resistance, and quantitative insulin-sensitivity check index) and ovarian cancer risk. Study selection, data extraction and an assessment of risk of bias were performed independently by three researchers. The associations between IR markers and ovarian cancer were quantified as mean differences (MDs) or standardized MDs (SMDs) and their 95% CIs using random-effects models.ResultsFourteen case-control studies satisfied our inclusion criteria (n = 8130). There was little information on IR markers with the exception of the IGF system. Ovarian cancer was associated with lower IGF-1 levels (SMD −0.43 ng/mL, 95% CI −0.67 to −0.18; p = 0.0006), and lower IGFBP-3 levels (SMD −0.11 ng/mL, 95% CI −0.21 to −0.00; p = 0.04). However, ovarian cancer was associated with higher levels of IGFBP-2 and IGFBP-1 (MD 527.3 ng/mL, 95%CI 473.6, 581.0; p < 0.00001, and MD 3.47 ng/mL, 95%CI 1.42, 5.52; p = 0.0009 respectively). Subgroup analyses by menopausal status and age (≤55 vs >55y) for IGF-1 and IGFBP-3 showed the subgroups were similar, although heterogeneity remained high.ConclusionThe evidence suggests that levels of IGF-1 and IGFBP-3 are lower in patients with ovarian cancer. In contrast, higher levels of IGBP-2 and IGBP-1 are found in patients with ovarian cancer.     

Mobile bearing dislocation in lateral unicompartmental knee replacement

Despite the theoretical advantages of mobile bearings for lateral unicompartmental replacement (UKR), the failure rate in the initial published series of lateral Oxford UKR's was unacceptably high. The main cause of failure was bearing dislocation. To address this problem we first modified the surgical technique and then introduced a new design with a convex domed tibial plateau. This paper presents the results of these changes.In the original series (n = 53), implanted using a standard open approach, there were six dislocations, all of which occurred in the first year. Five of the dislocations were primary and one was secondary to trauma. In the second series (n = 65), with the modified technique, there were three dislocations, all of which were primary and occurred in the second and third year. In the third series (n = 101, 69 with a minimum 1-year follow-up), with the modified technique and the domed tibial plateau, there was one dislocation which was secondary to trauma and occurred in the second year. At 4 years the dislocation rates in the three series were 11%, 5% and 1.7% and the primary dislocation rates were 10%, 5% and 0%. Both the overall and the primary dislocation rates were significantly different (p = 0.04 and p = 0.03) in the different series.The combination of the modified surgical technique and new design with a domed tibial component appears to have reduced the early dislocation rate to an acceptable level.