Effects of Breastfeeding on Respiratory Symptoms in Infancy.

OBJECTIVE To assess the impact of potential risk factors on the development of respiratory symptoms and their specific modification by breastfeeding in infants in the first year of life. STUDY DESIGN We prospectively studied 436 healthy term infants from the Bern-Basel Infant Lung Development cohort. The breastfeeding status, and incidence and severity of respiratory symptoms (score) were assessed weekly by telephone interview during the first year of life. Risk factors (eg, pre- and postnatal smoking exposure, mode of delivery, gestational age, maternal atopy, and number of older siblings) were obtained using standardized questionnaires. Weekly measurements of particulate matter <10 μg were provided by local monitoring stations. The associations were investigated using generalized additive mixed model with quasi Poisson distribution. RESULTS Breastfeeding reduced the incidence and severity of the respiratory symptom score mainly in the first 27 weeks of life (risk ratio 0.70; 95% CI 0.55-0.88). We found a protective effect of breastfeeding in girls but not in boys. During the first 27 weeks of life, breastfeeding attenuated the effects of maternal smoking during pregnancy, gestational age, and cesarean delivery on respiratory symptoms. There was no evidence for an interaction between breastfeeding and maternal atopy, number of older siblings, child care attendance, or particulate matter <10 μg. CONCLUSIONS This study shows the risk-specific effect of breastfeeding on respiratory symptoms in early life using the comprehensive time-series approach.

A novel colourimetric technique to assess chewing function using two-coloured specimens: Validation and application

OBJECTIVES Chewing efficiency may be evaluated using cohesive specimen, especially in elderly or dysphagic patients. The aim of this study was to evaluate three two-coloured chewing gums for a colour-mixing ability test and to validate a new purpose built software (ViewGum©). METHODS Dentate participants (dentate-group) and edentulous patients with mandibular two-implant overdentures (IOD-group) were recruited. First, the dentate-group chewed three different types of two-coloured gum (gum1-gum3) for 5, 10, 20, 30 and 50 chewing cycles. Subsequently the number of chewing cycles with the highest intra- and inter-rater agreement was determined visually by applying a scale (SA) and opto-electronically (ViewGum©, Bland-Altman analysis). The ViewGum© software determines semi-automatically the variance of hue (VOH); inadequate mixing presents with larger VOH than complete mixing. Secondly, the dentate-group and the IOD-group were compared. RESULTS The dentate-group comprised 20 participants (10 female, 30.3±6.7 years); the IOD-group 15 participants (10 female, 74.6±8.3 years). Intra-rater and inter-rater agreement (SA) was very high at 20 chewing cycles (95.00-98.75%). Gums 1-3 showed different colour-mixing characteristics as a function of chewing cycles, gum1 showed a logarithmic association; gum2 and gum3 demonstrated more linear behaviours. However, the number of chewing cycles could be predicted in all specimens from VOH (all p<0.0001, mixed linear regression models). Both analyses proved discriminative to the dental state. CONCLUSION ViewGum© proved to be a reliable and discriminative tool to opto-electronically assess chewing efficiency, given an elastic specimen is chewed for 20 cycles and could be recommended for the evaluation of chewing efficiency in a clinical and research setting. CLINICAL SIGNIFICANCE Chewing is a complex function of the oro-facial structures and the central nervous system. The application of the proposed assessments of the chewing function in geriatrics or special care dentistry could help visualising oro-functional or dental comorbidities in dysphagic patients or those suffering from protein-energy malnutrition.

Prospective longitudinal study of subcortical brain volumes in individuals at high familial risk of mood disorders with or without subsequent onset of depression

Subcortical volumetric brain abnormalities have been observed in mood disorders. However, it is unknown whether these reflect adverse effects predisposing to mood disorders or emerge at illness onset. Magnetic resonance imaging was conducted at baseline and after two years in 111 initially unaffected young adults at increased risk of mood disorders because of a close family history of bipolar disorder and 93 healthy controls (HC). During the follow-up, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the others remaining well (HR-well). Volumes of the lateral ventricles, caudate, putamen, pallidum, thalamus, hippocampus and amygdala were extracted for each hemisphere. Using linear mixed-effects models, differences and longitudinal changes in subcortical volumes were investigated between groups (HC, HR-MDD, HR-well). There were no significant differences for any subcortical volume between groups controlling for multiple testing. Additionally, no significant differences emerged between groups over time. Our results indicate that volumetric subcortical brain abnormalities of these regions using the current method appear not to form familial trait markers for vulnerability to mood disorders in close relatives of bipolar disorder patients over the two-year time period studied. Moreover, they do not appear to reduce in response to illness onset at least for the time period studied.

A longitudinal three-center study of dental arch relationship in patients with bilateral cleft lip and palate

OBJECTIVE: To compare and evaluate longitudinally the dental arch relationships from 4.5 to 13.5 years of age with the Bauru-BCLP Yardstick in a large sample of patients with bilateral cleft lip and palate (BCLP). DESIGN: Retrospective longitudinal intercenter outcome study. PATIENTS: Dental casts of 204 consecutive patients with complete BCLP were evaluated at 6, 9, and 12 years of age. All models were identified only by random identification numbers. SETTING: Three cleft palate centers with different treatment protocols. MAIN OUTCOME MEASURES: Dental arch relationships were categorized with the Bauru-BCLP yardstick. Increments for each interval (from 6 to 9 years, 6 to 12 years, and 9 to 12 years) were analyzed by logistic and linear regression models. RESULTS: There were no significant differences in outcome measures between the centers at age 12 or at age 9. At age 6, center B showed significantly better results (p=.027), but this difference diminished as the yardstick score for this group increased over time (linear regression analysis), the difference with the reference category (center C, boys) for the intervals 6 to 12 and 9 to 12 years being 10.4% (p=.041) and 12.9% (p=.009), respectively. CONCLUSIONS: Despite different treatment protocols, dental arch relationships in the three centers were comparable in final scores at age 9 and 12 years. Delaying hard palate closure and employing infant orthopedics did not appear to be advantageous in the long run. Premaxillary osteotomy employed in center B appeared to be associated with less favorable development of the dental arch relationship between 9 and 12 years.

Sonographic follow-up of patients with carpal tunnel syndrome undergoing surgical or nonsurgical treatment: prospective cohort study

Purpose To compare changes in the largest cross-sectional area (CSA) of the median nerve in wrists undergoing surgical decompression with changes in wrists undergoing non-surgical treatment of carpal tunnel syndrome (CTS). Methods This study was a prospective cohort study in 55 consecutive patients with 78 wrists with established CTS, including 60 wrists treated with surgical decompression and 18 wrists with non-surgical treatment. A sonographic examination was scheduled before and 4 months after initiation of treatment. We compared changes in CSA of the median nerve between wrists with surgical treatment and wrists with non-surgical treatment using linear regression models. Results Decreases in CSA of the median nerve were more pronounced in wrists with CTS release than in wrists undergoing nonsurgical treatment (difference in means, 1.0 mm2; 95% confidence interval, 0.3–1.8 mm2). Results were robust to the adjustment for age, gender, and neurological severity at baseline. Among wrists with CTS release, those with postoperative CSA of 10 mm2 or less tended to have better clinical outcomes than those with postoperative CSA of greater than 10 mm2 (p=.055). Postoperative sonographic workup in the 3 patients with unfavorable outcome or recurrence identified likely causes for treatment failure in 2 patients. Conclusions In this observational study, surgical decompression was associated with a greater decrease in median nerve CSA than was nonsurgical treatment. Smaller postoperative CSAs may be associated with better clinical outcomes. Additional randomized trials are necessary to determine the optimal treatment strategy in different subgroups of patients with CTS. Type of study/level of evidence Therapeutic III.

Predictors and overestimation of recalled mobile phone use among children and adolescents

A growing body of literature addresses possible health effects of mobile phone use in children and adolescents by relying on the study participants' retrospective reconstruction of mobile phone use. In this study, we used data from the international case-control study CEFALO to compare self-reported with objectively operator-recorded mobile phone use. The aim of the study was to assess predictors of level of mobile phone use as well as factors that are associated with overestimating own mobile phone use. For cumulative number and duration of calls as well as for time since first subscription we calculated the ratio of self-reported to operator-recorded mobile phone use. We used multiple linear regression models to assess possible predictors of the average number and duration of calls per day and logistic regression models to assess possible predictors of overestimation. The cumulative number and duration of calls as well as the time since first subscription of mobile phones were overestimated on average by the study participants. Likelihood to overestimate number and duration of calls was not significantly different for controls compared to cases (OR=1.1, 95%-CI: 0.5 to 2.5 and OR=1.9, 95%-CI: 0.85 to 4.3, respectively). However, likelihood to overestimate was associated with other health related factors such as age and sex. As a consequence, such factors act as confounders in studies relying solely on self-reported mobile phone use and have to be considered in the analysis.

Five-year results of a randomized controlled clinical trial comparing zirconia and titanium abutments supporting single-implant crowns in canine and posterior regions

OBJECTIVES: To test the survival rates, and the technical and biological complication rates of customized zirconia and titanium abutments 5 years after crown insertion. MATERIAL AND METHODS: Twenty-two patients with 40 single implants in maxillary and mandibular canine and posterior regions were included. The implant sites were randomly assigned to zirconia abutments supporting all-ceramic crowns or titanium abutments supporting metal-ceramic crowns. Clinical examinations were performed at baseline, and at 6, 12, 36 and 60 months of follow-up. The abutments and reconstructions were examined for technical and/or biological complications. Probing pocket depth (PPD), plaque control record (PCR) and Bleeding on Probing (BOP) were assessed at abutments (test) and analogous contralateral teeth (control). Radiographs of the implants revealed the bone level (BL) on mesial (mBL) and distal sides (dBL). Data were statistically analyzed with nonparametric mixed models provided by Brunner and Langer and STATA (P < 0.05). RESULTS: Eighteen patients with 18 zirconia and 10 titanium abutments were available at a mean follow-up of 5.6 years (range 4.5-6.3 years). No abutment fracture or loss of a reconstruction occurred. Hence, the survival rate was 100% for both. Survival of implants supporting zirconia abutments was 88.9% and 90% for implants supporting titanium abutments. Chipping of the veneering ceramic occurred at three metal-ceramic crowns supported by titanium abutments. No significant differences were found at the zirconia and titanium abutments for PPD (meanPPD(ZrO2) 3.3 ± 0.6 mm, mPPD(T) (i) 3.6 ± 1.1 mm), PCR (mPCR(Z) (rO) (2) 0.1 ± 0.3, mPCR(T) (i) 0.3 ± 0.2) and BOP (mBOP(Z) (rO) (2) 0.5 ± 0.3, mBOP(T) (i) 0.6 ± 0.3). Moreover, the BL was similar at implants supporting zirconia and titanium abutments (mBL(Z) (rO) (2) 1.8 ± 0.5, dBL(Z) (rO) (2) 2.0 ± 0.8; mBL(T) (i) 2.0 ± 0.8, dBL(T) (i) 1.9 ± 0.8). CONCLUSIONS: There were no statistically or clinically relevant differences between the 5-year survival rates, and the technical and biological complication rates of zirconia and titanium abutments in posterior regions.

Do Central Hypersensitivity and Altered Pain Modulation Predict the Course of Chronic Low Back and Neck Pain?

OBJECTIVES:: Widespread central hypersensitivity and altered conditioned pain modulation (CPM) have been documented in chronic pain conditions. Information on their prognostic values is limited. This study tested the hypothesis that widespread central hypersensitivity (WCH) and altered CPM, assessed during the chronic phase of low back and neck pain, predict poor outcome. METHODS:: A total of 169 consecutive patients with chronic low back or neck pain, referred to the pain clinic during 1 year, were analyzed. Pressure pain tolerance threshold at the second toe and tolerance time during cold pressor test at the hand assessed WCH. CPM was measured by the change in pressure pain tolerance threshold (test stimulus) after cold pressor test (conditioning stimulus). A structured telephone interview was performed 12 to 15 months after testing to record outcome parameters. Linear regression models were used, with average and maximum pain intensity of the last 24 hours at follow-up as endpoints. Multivariable analyses included sex, age, catastrophizing scale, Beck Depression Inventory, pain duration, intake of opioids, and type of pain syndrome. RESULTS:: Statistically significant reductions from baseline to follow-up were observed in pain intensity (P<0.001). No evidence for an association between the measures of WCH or CPM and intensity of chronic pain at follow-up was found. DISCUSSION:: A major predictive value of the measures that we used is unlikely. Future studies adopting other assessment modalities and possibly standardized treatments are needed to further elucidate the prognostic value of WCH and altered CPM in chronic pain.

Physical activity intensity and surrogate markers for cardiovascular health in adolescents

We examined the impact of physical activity (PA) on surrogate markers of cardiovascular health in adolescents. 52 healthy students (28 females, mean age 14.5 ± 0.7 years) were investigated. Microvascular endothelial function was assessed by peripheral arterial tonometry to determine reactive hyperemic index (RHI). Vagal activity was measured using 24 h analysis of heart rate variability [root mean square of successive normal-to-normal intervals (rMSSD)]. Exercise testing was performed to determine peak oxygen uptake ([Formula: see text]) and maximum power output. PA was assessed by accelerometry. Linear regression models were performed and adjusted for age, sex, skinfolds, and pubertal status. The cohort was dichotomized into two equally sized activity groups (low vs. high) based on the daily time spent in moderate-to-vigorous PA (MVPA, 3,000-5,200 counts(.)min(-1), model 1) and vigorous PA (VPA, >5,200 counts(.)min(-1), model 2). MVPA was an independent predictor for rMSSD (β = 0.448, P = 0.010), and VPA was associated with maximum power output (β = 0.248, P = 0.016). In model 1, the high MVPA group exhibited a higher vagal tone (rMSSD 49.2 ± 13.6 vs. 38.1 ± 11.7 ms, P = 0.006) and a lower systolic blood pressure (107.3 ± 9.9 vs. 112.9 ± 8.1 mmHg, P = 0.046). In model 2, the high VPA group had higher maximum power output values (3.9 ± 0.5 vs. 3.4 ± 0.5 W kg(-1), P = 0.012). In both models, no significant differences were observed for RHI and [Formula: see text]. In conclusion, in healthy adolescents, PA was associated with beneficial intensity-dependent effects on vagal tone, systolic blood pressure, and exercise capacity, but not on microvascular endothelial function.

A prospective study of the impact of air pollution on respiratory symptoms and infections in infants

Rationale: There is increasing evidence that short-term exposure to air pollution has a detrimental effect on respiratory health, but data from healthy populations, particularly infants, are scarce. Objectives: To assess the association of air pollution with frequency and severity of respiratory symptoms and infections measured weekly in healthy infants. Methods: In a prospective birth cohort of 366 infants of unselected mothers, respiratory health was assessed weekly by telephone interviews during the first year of life (19,106 total observations). Daily mean levels of particulate matter (PM10), nitrogen dioxide (NO2), and ozone (O3) were obtained from local monitoring stations. We determined the association of the preceding week's pollutant levels with symptom scores and respiratory tract infections using a generalized additive mixed model with an autoregressive component. In addition, we assessed whether neonatal lung function influences this association and whether duration of infectious episodes differed between weeks with normal PM10 and weeks with elevated levels. Measurements and Main Results: We found a significant association between air pollution and respiratory symptoms, particularly in the week after respiratory tract infections (risk ratio, 1.13 [1.02-1.24] per 10 μg/m(3) PM10 levels) and in infants with premorbid lung function. During times of elevated PM10 (>33.3 μg/m(3)), duration of respiratory tract infections increased by 20% (95% confidence interval, 2-42%). Conclusions: Exposure to even moderate levels of air pollution was associated with increased respiratory symptoms in healthy infants. Particularly in infants with premorbid lung function and inflammation, air pollution contributed to longer duration of infectious episodes with a potentially large socioeconomic impact.

Clinical and molecular characterization of the potential CF disease modifier syntaxin 1A

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator gene (CFTR). Disease severity in CF varies greatly, and sibling studies strongly indicate that genes other than CFTR modify disease outcome. Syntaxin 1A (STX1A) has been reported as a negative regulator of CFTR and other ion channels. We hypothesized that STX1A variants act as a CF modifier by influencing the remaining function of mutated CFTR. We identified STX1A variants by genomic resequencing patients from the Bernese CF Patient Data Registry and applied linear mixed model analysis to establish genotype-phenotype correlations, revealing STX1A rs4363087 (c.467-38A>G) to significantly influence lung function. The same STX1A risk allele was recognized in the European CF Twin and Sibling Study (P=0.0027), demonstrating that the genotype-phenotype association of STX1A to CF disease severity is robust enough to allow replication in two independent CF populations. rs4363087 is in linkage disequilibrium to the exonic variant rs2228607 (c.204C>T). Considering that neither rs4363087 nor rs2228607 changes the amino-acid sequence of STX1A, we investigated their effects on mRNA level. We show that rs2228607 reinforces aberrant splicing of STX1A mRNA, leading to nonsense-mediated mRNA decay. In conclusion, we demonstrate the clinical relevance of STX1A variants in CF, and evidence the functional relevance of STX1A variant rs2228607 at molecular level. Our findings show that genes interacting with CFTR can modify CF disease progression.European Journal of Human Genetics advance online publication, 10 April 2013; doi:10.1038/ejhg.2013.57.

Identification of SNPs in the cystic fibrosis interactome influencing pulmonary progression in cystic fibrosis

There is growing evidence that the great phenotypic variability in patients with cystic fibrosis (CF) not only depends on the genotype, but apart from a combination of environmental and stochastic factors predominantly also on modifier gene effects. It has been proposed that genes interacting with CF transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) are potential modifiers. Therefore, we assessed the impact of single-nucleotide polymorphisms (SNPs) of several of these interacters on CF disease outcome. SNPs that potentially alter gene function were genotyped in 95 well-characterized p.Phe508del homozygous CF patients. Linear mixed-effect model analysis was used to assess the relationship between sequence variants and the repeated measurements of lung function parameters. In total, we genotyped 72 SNPs in 10 genes. Twenty-five SNPs were used for statistical analysis, where we found strong associations for one SNP in PPP2R4 with the lung clearance index (P ≤ 0.01), the specific effective airway resistance (P ≤ 0.005) and the forced expiratory volume in 1 s (P ≤ 0.005). In addition, we identified one SNP in SNAP23 to be significantly associated with three lung function parameters as well as one SNP in PPP2R1A and three in KRT19 to show a significant influence on one lung function parameter each. Our findings indicate that direct interacters with CFTR, such as SNAP23, PPP2R4 and PPP2R1A, may modify the residual function of p.Phe508del-CFTR while variants in KRT19 may modulate the amount of p.Phe508del-CFTR at the apical membrane and consequently modify CF disease.

Stable virulence levels in the HIV epidemic of Switzerland over two decades

OBJECTIVE: To determine whether the virulence of HIV-1 has been changing since its introduction into Switzerland. DESIGN: A prospective cohort study of HIV-1 infected individuals with well-characterized pre-therapy disease history. METHODS: To minimize the effect of recently imported viruses and ethnicity-associated host factors, the analysis was restricted to the white, north-west-European majority population of the cohort. Virulence was characterized by the decline slope of the CD4 cell count (n = 817 patients), the decline slope of the CD4:CD8 ratio (n = 815 patients) and the viral setpoint (n = 549 patients) in untreated patients with sufficient data points. Linear regression models were used to detect correlations between the date of diagnosis (ranging between 1984 and 2003) and the virulence markers, controlling for gender, exposure category, age and CD4 cell count at entry. RESULTS: We found no correlation between any of the virulence markers and the date of diagnosis. Inspection of short-term trends confirmed that virulence has fluctuated around a stable level over time. CONCLUSIONS: The lack of long-term time trends in the virulence markers indicates that HIV-1 is not evolving towards increasing or decreasing virulence at a perceptible rate. Both highly virulent and attenuated strains have apparently been unable to spread at the population level. This result suggests that either the evolution of virulence may be slow or inhibited due to evolutionary constraints, or HIV-1 may have already evolved to optimal virulence in the human host.

Sleepless night, the moon is bright: longitudinal study of lunar phase and sleep

Popular belief holds that the lunar cycle affects human physiology, behaviour and health. We examined the influence of moon phase on sleep duration in a secondary analysis of a feasibility study of mobile telephone base stations and sleep quality. We studied 31 volunteers (18 women and 13 men, mean age 50 years) from a suburban area of Switzerland longitudinally over 6 weeks, including two full moons. Subjective sleep duration was calculated from sleep diary data. Data were analysed using multiple linear regression models with random effects. Mean sleep duration was 6 h 49 min. Subjective sleep duration varied with the lunar cycle, from 6 h 41 min at full moon to 7 h 00 min at new moon (P < 0.001). Average sleep duration was shortened by 68 min during the week compared with weekends (P < 0.001). Men slept 17 min longer than women (P < 0.001) and sleep duration decreased with age (P < 0.001). There was also evidence that rating of fatigue in the morning was associated with moon phase, with more tiredness (P = 0.027) at full moon. The study was designed for other purposes and the association between lunar cycle and sleep duration will need to be confirmed in further studies.

Endocrine symptom assessment in women with breast cancer: what a simple "yes" means

GOALS OF WORK: To investigate the self-reported symptoms related to endocrine therapy in women with early or advanced breast cancer and the impact of these symptoms on quality of life (QL) indicators. MATERIALS AND METHODS: Symptom occurrence was assessed by the Checklist for Patients on Endocrine Therapy (C-PET) and symptom intensity was assessed by linear analogue self-assessment (LASA) indicators. Patients also responded to global LASA indicators for physical well-being, mood, coping effort and treatment burden. Associations between symptoms and these indicators were analysed by linear regression models. MAIN RESULTS: Among 373 women, the distribution of symptom intensity showed considerable variation in patients reporting a symptom as present. Even though patients recorded a symptom as absent, some patients reported having experienced that symptom when responding to symptom intensity, as seen for decreased sex drive, tiredness and vaginal dryness. Six of 13 symptoms and lower age had a detrimental impact on the global indicators, particularly tiredness and irritability. CONCLUSIONS: Patients' experience of endocrine symptoms needs to be considered both in patient care and research, when interpreting the association between symptoms and QL.