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The association between lower birth weight and increased disease risk in adulthood has drawn attention to the physiological processes that shape the gestational environment. We implement genome-wide transcriptional profiling of maternal blood samples to identify subsets of genes and associated transcription control pathways that predict offspring birth weight. Female participants (N = 178, mean = 27.0 years) in a prospective observational birth cohort study were contacted between 2009 and 2014 to identify new pregnancies. An in-home interview was scheduled for early in the third trimester (mean = 30.3 weeks) to collect pregnancy-related information and a blood sample, and birth weight was measured shortly after delivery. Transcriptional activity in white blood cells was determined with a whole-genome gene expression direct hybridization assay. Fifty transcripts were differentially expressed in association with offspring birth weight, with 18 up-regulated in relation to lower birth weight, and 32 down-regulated. Examination of transcription control pathways identified increased activity of NF-κB, AP-1, EGR1, EGR4, and Gfi families, and reduced the activity of CEBP, in association with lower birth weight. Transcript origin analyses identified non-classical CD16+ monocytes, CD1c+ myeloid dendritic cells, and neutrophils as the primary cellular mediators of differential gene expression. These results point toward a systematic regulatory shift in maternal white blood cell activity in association with lower offspring birth weight, and they suggest that analyses of gene expression during gestation may provide insight into regulatory and cellular mechanisms that influence birth outcomes.
Background: To attain the most comprehensive view of the quality of life (QoL) of a child with Duchenne Muscular Dystrophy (DMD), the completion of a pediatric QoL measure by the child and his/her parent and the assessment of QoL and health-related quality of life (HRQoL) as separate constructs is crucial. Previous QoL research has not assessed HRQoL as a separate construct. By using the Quality of My Life (QoML) questionnaire, our objective was to describe QoL and HRQoL in boys with DMD based on child-and parent-reports. Methods: Parent and child dyads identified via the Canadian Neuromuscular Disease Registry received QoML questionnaires (2013-2016). Children and parent-proxy each completed the QoL and HRQoL Visual Analog Scales. Responses were marked on a 10-cm line, with higher scores (max=10) reflecting higher QoL and HRQoL. Descriptive statistics were computed for child- and parent-reports of QoL and HRQoL at three time-points. Results: Mean(SD) QoL and HRQoL scores for child- and parent-reports were: 1) Baseline (n=20 dyads), 8.32(1.72) vs. 6.73(2.23) and 7.63(2.51) vs. 6.73(2.19); 2)18-months (n=10 dyads, n=9 dyads), 7.83(2.05) vs 7.66(1.66) and 7.62(2.41) vs 7.41(2.16); 3) 36-months (n=15 dyads) 7.38(2.00) vs. 6.99(1.77) and 7.19(2.70) vs. 6.76(2.26). Conclusions: Boys with DMD report higher QoL and HRQoL compared to their parents.
To establish high intake of free sugars and its related disease burden as a significant public health challenge in Australia.
We discuss five key actions to reduce intake of free sugars tailored to the Australian context. These strategies are informed by reviewing the global scientific evidence on the effectiveness of a range of policy responses to reduce intake of free sugars at the population level.
The five key actions to reduce population levels for intake of free sugars tailored to the Australian context include prioritising health in trade agreements and policy; introducing a fiscal policy supporting health and promoting food reformulation; regulating advertising and improving labelling; strengthening the current dietary guidelines; and encouraging healthy choices.
The adoption and implementation of the strategies discussed in the current commentary would aid in tackling the rising health burden from the intake of free sugars in Australia.
Introduction: Abdominal pain is one of the most frequent reasons for an emergency department (ED) visit. Most cases are functional and no therapy has proven effective. Our objective was to determine if hyoscine butylbromide (HBB) (BuscopanTM) is effective for children who present to the ED with functional abdominal pain. Methods: We conducted a randomized, blinded, superiority trial comparing HBB 10 mg plus acetaminophen placebo to oral acetaminophen 15 mg/kg (max 975 mg) plus HBB placebo using a double-dummy approach. We included children 8-17 years presenting to the ED at London Health Sciences Centre with colicky abdominal pain rated >40 mm on a 100 mm visual analog scale (VAS). The primary outcome was VAS pain score at 80 minutes post-administration. Secondary outcomes included adverse effects; caregiver satisfaction with pain management using a five-item Likert scale; recidivism and missed surgical diagnoses within 24-hours of discharge. Analysis was based on intention to treat. Results: We analyzed 225 participants (112 acetaminophen; 113 HBB). The mean (SD) age was 12.4 (3.0) years and 148/225 (65.8%) were females. Prior to enrollment, the median (IQR) duration of pain prior was 2 (4.5) hours and analgesia was provided to 101/225 (44.9%) of participants. The mean (SD) pre-intervention pain scores in the acetaminophen and HBB groups were 62.7 (15.9) mm and 60.3 (17.3) mm, respectively. At 80 minutes, the mean (SD) pain scores in the acetaminophen and HBB groups were 30.1 (28.8) mm and 29.4 (26.4) mm, respectively and there were no significant differences adjusting for pre-intervention scores (p = 0.96). The median (IQR) caregiver satisfaction was high in the acetaminophen [5 (2)] and HBB [5 (1)] groups (p = 0.79). The median (IQR) length of stay between acetaminophen [235 (101)] and HBB [234 (103)] was not significantly different (p = 0.53). The proportion of participants with a return visit for abdominal pain was 4/112 (3.5%) in the acetaminophen group and 6/113 (5.3%) in the HBB group. The most common adverse effect was nausea (9% in each group) and there were no significant differences in adverse effects between acetaminophen (26/112, 23.2%) and HBB (31/113, 27.4%) (p = 0.52). There were no missed surgical diagnoses. Conclusion: For children with presumed functional abdominal pain who present to the ED, both acetaminophen and HBB produce a clinically important (VAS < 30 mm) reduction in pain and should be routinely considered in this clinical setting.
Childhood maltreatment is associated with increased risk for most forms of psychopathology. We examine emotion dysregulation as a transdiagnostic mechanism linking maltreatment with general psychopathology. A sample of 262 children and adolescents participated; 162 (61.8%) experienced abuse or exposure to domestic violence. We assessed four emotion regulation processes (cognitive reappraisal, attention bias to threat, expressive suppression, and rumination) and emotional reactivity. Psychopathology symptoms were assessed concurrently and at a 2-year longitudinal follow-up. A general psychopathology factor (p factor), representing co-occurrence of psychopathology symptoms across multiple internalizing and externalizing domains, was estimated using confirmatory factor analysis. Maltreatment was associated with heightened emotional reactivity and greater use of expressive suppression and rumination. The association of maltreatment with attention bias varied across development, with maltreated children exhibiting a bias toward threat and adolescents a bias away from threat. Greater emotional reactivity and engagement in rumination mediated the longitudinal association between maltreatment and increased general psychopathology over time. Emotion dysregulation following childhood maltreatment occurs at multiple stages of the emotion generation process, in some cases varies across development, and serves as a transdiagnostic mechanism linking child maltreatment with general psychopathology.
Numerous studies have been conducted into the microstructural origin of the instability and unpredictability of various energetic materials. Some of these materials are RDX/HMX, Ammonium Perchlorate, Aluminum, etc. Many techniques both destructive and non-destructive have so far been utilized in an attempt to quatify the energetic properties of their composites. These composites may contain one or more energetic constituents in an elastomeric binder. Non-destructive X-ray characterization techniques have been successfully employed to measure several microstructural parameters. Previous studies have shown considerable differences among various production grade RDX. These studies reveal marked differences in the amounts of residual elastic strain and the distribution of dislocations (residual plastic strain) in the constituent RDX phase.
The focus of this study is to develop a technique for quantitative constituent phase analysis of solid-propellant (fuel) composites using conventional diffractometry. The use of a Curved Position Sensitive Detector (CPSD) greatly enhances the technique and allows real time applications in production environments. Through the use of computer based Systems and "user friendly" software the required Operator, skill and training have been considerably reduced. The CPSD System has been successfully used to quantify constituent phases (peak heights) and the amounts of residual elastic strain (peak shifts) in these molecular crystal powder mixtures.
It is envisioned that rapid, automated, non-destructive X-ray characterization techniques will greatly facilitate production based propellant quality control. A thorough understanding of the relationship between the energetics and microstructural parameters can also he obtained.
In several recently published phylogenetic analyses, two Lower Devonian taxa, Doliodus and Pucapampella, both fall on the chondrichthyan stem, very close to the base of ‘conventionally defined chondrichthyans’ (i.e., forms possessing tessellated mineralization of the cartilaginous endoskeleton). These two taxa nevertheless exhibit strongly discordant morphologies from each other. A summary of the anatomical data concerning these taxa is presented here, including new, as well as previously published, findings. A new family Pucapampellidae is erected, containing Pucapampella and a newly recognized genus from South Africa. Morphological evidence is summarized for the monophyly of crown elasmobranchs (sharks and rays), holocephalans (chimaeras) and other chondrichthyans. Based on these data, Doliodus and pucapampellids both fall outside the chondrichthyan crown, but their relative phylogenetic positions on the chondrichthyan stem are unclear. Pucapampellid interrelationships are particularly hard to assess because little is known beyond their cranial and visceral arch morphology and also because pucapampellids possess a suite of ontogenetically primitive (and thus potentially neotenic) features. By contrast, the phylogenetic position of Doliodus seems less elusive; it possessed an ‘acanthodian-like’ complex of dermal spines, including pectoral fin spines, prepectoral, admedian, and prepelvic spines, and possibly dorsal and pelvic fin spines, in conjunction with numerous ‘chondrichthyan-like’ endoskeletal features and a heterodont ‘sharklike’ dentition. Doliodus can be viewed as a quintessential component of the evolutionary transition between ‘acanthodians’ and ‘conventionally defined chondrichthyans’, leaving little doubt that the chondrichthyan total group includes ‘acanthodians’ (now widely perceived to be a paraphyletic group, populating the basal part of the chondrichthyan stem). Although Doliodus has been resolved as a basal member of the ‘conventionally defined chondrichthyans’, it could occupy a more basal position on the chondrichthyan stem.
The Japanese Murrelet Synthliboramphus wumizusume is a rare, globally ‘Vulnerable’ seabird, endemic to Japan and South Korea. However, little is known of its at-sea distribution, habitat or threats. We conducted several years of at-sea surveys around Japan to model Japanese Murrelet density in relation to habitat parameters, and make spatial predictions to assess the adequacy of the current Japanese marine Important Bird and Biodiversity Area (IBA) network for the species. During a five-year period, 3,485 km of at-sea surveys recorded 3,161 Japanese Murrelets around four breeding locations. Maximum murrelet group size was 90 individuals with a mean group size of 2.9 ± 4.2 individuals. Models of Japanese Murrelet at-sea density around the two largest breeding locations predicted that almost all murrelets occur within 30 km of the breeding colony and most within 10 km. Murrelets were predicted closer to the colony in May than in April and closer to the colony at a neritic colony than at an offshore island colony. Additionally, murrelets breeding on an offshore island colony also commuted to mainland neritic habitat for foraging. The marine habitat used by Japanese Murrelets differed between each of the four surveyed colonies, however oceanographic variables offered little explanatory power in models. Models with colony, month and year generated four foraging radii (9–39 km wide) containing murrelet densities of > 0.5 birds/km2. Using these radii the Japanese marine IBA network was found to capture between 95% and 25% of Japanese Murrelet at-sea habitat while breeding and appears appropriately configured to protect near-colony murrelet distributions. Given the range of marine habitats that breeding murrelets inhabit, our simple models offer an applicable method for predicting to unsampled colonies and generating ecologically-informed seaward extension radii. However, data on colony populations and further at-sea surveys are necessary to refine models and improve predictions.
Large efforts have been deployed in developing methods to estimate methane emissions from cattle. For large scale applications, accurate and inexpensive methane predictors are required. Within a livestock precision farming context, the objective of this work was to integrate real-time data on animal feeding behaviour with an in silico model for predicting the individual dynamic pattern of methane emission in cattle. The integration of real-time data with a mathematical model to predict variables that are not directly measured constitutes a software sensor. We developed a dynamic parsimonious grey-box model that uses as predictor variables either dry matter intake (DMI) or the intake time (IT). The model is described by ordinary differential equations.
Model building was supported by experimental data of methane emissions from respiration chambers. The data set comes from a study with finishing beef steers (cross-bred Charolais and purebred Luing finishing). Dry matter intake and IT were recorded using feed bins. For research purposes, in this work, our software sensor operated off-line. That is, the predictor variables (DMI, IT) were extracted from the recorded data (rather than from an on-line sensor). A total of 37 individual dynamic patterns of methane production were analyzed. Model performance was assessed by concordance analysis between the predicted methane output and the methane measured in respiration chambers. The model predictors DMI and IT performed similarly with a Lin’s concordance correlation coefficient (CCC) of 0.78 on average. When predicting the daily methane production, the CCC was 0.99 for both DMI and IT predictors. Consequently, on the basis of concordance analysis, our model performs very well compared with reported literature results for methane proxies and predictive models. As IT measurements are easier to obtain than DMI measurements, this study suggests that a software sensor that integrates our in silico model with a real-time sensor providing accurate IT measurements is a viable solution for predicting methane output in a large scale context.
Background: Unwanted intrusive thoughts of intentionally harming one's infant (intrusive harm thoughts) are common distressing experiences among postpartum mothers and fathers. Aim: To understand infant crying as a stimulus for intrusive harm thoughts and associated emotional responses in prepartum and postpartum mothers and fathers in response to infant cry. Method: Following completion of self-report measures of negative mood and anger, prepartum (n = 48) and postpartum (n = 44) samples of mother and father pairs completed 10 minutes of listening to audio-recorded infant crying. Post-test questionnaires assessed harm thoughts, negative emotions, urges to comfort and flee, and thoughts of shaking as a soothing or coping strategy. Results: One quarter of prepartum and 44% of postpartum parents reported intrusive infant-related harm thoughts following crying. Mothers and fathers did not differ in the likelihood of reporting harm thoughts, nor in the number of thoughts reported. Women reported more internalizing emotions compared with men. Hostile emotions were stronger among postpartum parents, and parents reporting harm thoughts. All parents reported strong urges to comfort the infant. Urges to flee were stronger among parents who reported harm thoughts. The likelihood of using infant shaking as a soothing or coping strategy was minimally endorsed, albeit more strongly by fathers and parents who also reported harm thoughts. Conclusions: In response to crying, harm thoughts are common and are associated with hostile emotions, urges to flee, and increased thoughts of using infant shaking. Reassuringly, the number of participants considering infant shaking as a strategy for soothing or for coping with a crying infant was low.
Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal–infant bonding. On the basis of expected physiology, maternal–infant bonding may be safe for select cardiac diagnoses.
This is a single-centre study to assess safety of maternal–infant bonding in prenatal CHD.
In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001).
Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.
Behavioral and psychological symptoms of dementia (BPSD) are nearly universal in dementia, a condition occurring in more than 40 million people worldwide. BPSD present a considerable treatment challenge for prescribers and healthcare professionals. Our purpose was to prioritize existing and emerging treatments for BPSD in Alzheimer's disease (AD) overall, as well as specifically for agitation and psychosis.
International Delphi consensus process. Two rounds of feedback were conducted, followed by an in-person meeting to ratify the outcome of the electronic process.
2015 International Psychogeriatric Association meeting.
Expert panel comprised of 11 international members with clinical and research expertise in BPSD management.
Consensus outcomes showed a clear preference for an escalating approach to the management of BPSD in AD commencing with the identification of underlying causes. For BPSD overall and for agitation, caregiver training, environmental adaptations, person-centered care, and tailored activities were identified as first-line approaches prior to any pharmacologic approaches. If pharmacologic strategies were needed, citalopram and analgesia were prioritized ahead of antipsychotics. In contrast, for psychosis, pharmacologic options, and in particular, risperidone, were prioritized following the assessment of underlying causes. Two tailored non-drug approaches (DICE and music therapy) were agreed upon as the most promising non-pharmacologic treatment approaches for BPSD overall and agitation, with dextromethorphan/quinidine as a promising potential pharmacologic candidate for agitation. Regarding future treatments for psychosis, the greatest priority was placed on pimavanserin.
This international consensus panel provided clear suggestions for potential refinement of current treatment criteria and prioritization of emerging therapies.
To determine which healthcare worker (HCW) roles and patient care activities are associated with acquisition of vancomycin-resistant Enterococcus (VRE) on HCW gloves or gowns after patient care, as a surrogate for transmission to other patients.
Prospective cohort study.
Medical and surgical intensive care units at a tertiary-care academic institution.
VRE-colonized patients on Contact Precautions and their HCWs.
Overall, 94 VRE-colonized patients and 469 HCW–patient interactions were observed. Research staff recorded patient care activities and cultured HCW gloves and gowns for VRE before doffing and exiting patient room.
VRE were isolated from 71 of 469 HCWs’ gloves or gowns (15%) following patient care. Occupational/physical therapists, patient care technicians, nurses, and physicians were more likely than environmental services workers and other HCWs to have contaminated gloves or gowns. Compared to touching the environment alone, the odds ratio (OR) for VRE contamination associated with touching both the patient (or objects in the immediate vicinity of the patient) and environment was 2.78 (95% confidence interval [CI], 0.99–0.77) and the OR associated with touching only the patient (or objects in the immediate vicinity) was 3.65 (95% CI, 1.17–11.41). Independent risk factors for transmission of VRE to HCWs were touching the patient’s skin (OR, 2.18; 95% CI, 1.15–4.13) and transferring the patient into or out of bed (OR, 2.66; 95% CI, 1.15–6.43).
Patient contact is a major risk factor for HCW contamination and subsequent transmission. Interventions should prioritize contact precautions and hand hygiene for HCWs whose activities involve touching the patient.
Understanding how critical sow live-weight and back-fat depth during gestation are in ensuring optimum sow productivity is important. The objective of this study was to quantify the association between sow parity, live-weight and back-fat depth during gestation with subsequent sow reproductive performance. Records of 1058 sows and 13 827 piglets from 10 trials on two research farms between the years 2005 and 2015 were analysed. Sows ranged from parity 1 to 6 with the number of sows per parity distributed as follows: 232, 277, 180, 131, 132 and 106, respectively. Variables that were analysed included total born (TB), born alive (BA), piglet birth weight (BtWT), pre-weaning mortality (PWM), piglet wean weight (WnWT), number of piglets weaned (Wn), wean to service interval (WSI), piglets born alive in subsequent farrowing and sow lactation feed intake. Calculated variables included the within-litter CV in birth weight (LtV), pre-weaning growth rate per litter (PWG), total litter gain (TLG), lactation efficiency and litter size reared after cross-fostering. Data were analysed using linear mixed models accounting for covariance among records. Third and fourth parity sows had more (P<0.05) TB, BA and heavier BtWT compared with gilts and parity 6 sow contemporaries. Parities 2 and 3 sows weaned more (P<0.05) piglets than older sows. These piglets had heavier (P<0.05) birth weights than those from gilt litters. LtV and PWM were greater (P<0.01) in litters born to parity 5 sows than those born to younger sows. Sow live-weight and back-fat depth at service, days 25 and 50 of gestation were not associated with TB, BA, BtWT, LtV, PWG, WnWT or lactation efficiency (P>0.05). Heavier sow live-weight throughout gestation was associated with an increase in PWM (P<0.01) and reduced Wn and lactation feed intake (P<0.05). Deeper back-fat in late gestation was associated with fewer (P<0.05) BA but heavier (P<0.05) BtWT, whereas deeper back-fat depth throughout gestation was associated with reduced (P<0.01) lactation feed intake. Sow back-fat depth was not associated with LtV, PWG, TLG, WSI or piglets born alive in subsequent farrowing (P>0.05). In conclusion, this study showed that sow parity, live-weight and back-fat depth can be used as indicators of reproductive performance. In addition, this study also provides validation for future development of a benchmarking tool to monitor and improve the productivity of modern sow herd.
Posttraumatic stress disorder (PTSD) and stress/trauma exposure are cross-sectionally associated with advanced DNA methylation age relative to chronological age. However, longitudinal inquiry and examination of associations between advanced DNA methylation age and a broader range of psychiatric disorders is lacking. The aim of this study was to examine if PTSD, depression, generalized anxiety, and alcohol-use disorders predicted acceleration of DNA methylation age over time (i.e. an increasing pace, or rate of advancement, of the epigenetic clock).
Genome-wide DNA methylation and a comprehensive set of psychiatric symptoms and diagnoses were assessed in 179 Iraq/Afghanistan war veterans who completed two assessments over the course of approximately 2 years. Two DNA methylation age indices (Horvath and Hannum), each a weighted index of an array of genome-wide DNA methylation probes, were quantified. The pace of the epigenetic clock was operationalized as change in DNA methylation age as a function of time between assessments.
Analyses revealed that alcohol-use disorders (p = 0.001) and PTSD avoidance and numbing symptoms (p = 0.02) at Time 1 were associated with an increasing pace of the epigenetic clock over time, per the Horvath (but not the Hannum) index of cellular aging.
This is the first study to suggest that posttraumatic psychopathology is longitudinally associated with a quickened pace of the epigenetic clock. Results raise the possibility that accelerated cellular aging is a common biological consequence of stress-related psychopathology, which carries implications for identifying mechanisms of stress-related cellular aging and developing interventions to slow its pace.
Background: Serine deficiency disorders can result from deficiency in one of three enzymes. Deficiency of the second enzyme in the serine biosynthesis pathway, 3-phosphoserine aminotransferase (PSAT), has been reported in two siblings when the eldest was investigated for acquired microcephaly, progressive spasticity and intractable epilepsy. Methods: Our patient had neurological symptoms apparent at birth. Fetal magnetic resonance imaging (MRI) at 35 weeks gestation demonstrated microencephaly and simplification of the the gyration (anterior>posterior) which was confirmed upon subsequent post-natal MRI. Congenital microcephaly was apparent at birth. Results: PSAT deficiency was confirmed when exome sequencing identified biallelic mutations in PSAT1; c.44C>T, p.Ala15Val and; c.432delA, p.Pro144fs and biochemical testing noted low plasma serine 22 mcmol/L (normal 83-212 mcmol/L) and low CSF serine 10 mcmol/L (normal 22-61 mcmol/L). Despite oral serine and glycine supplementation at 4 months old the patient showed little neurodevelopmental progress and developed epileptic spasms at 10 months old. Serological testing for TORCH infections was negative. Conclusions: PSAT deficiency should be considered for patients with congenital microcephaly. Although further characterization of MRI findings in other patients is required, microencephaly with simplified gyral pattern could provide imaging clues for this rare metabolic disorder.
Background: Longitudinal data on health-related quality of life (HRQOL) and fatigue in paediatric Duchenne muscular dystrophy (DMD) are limited. Recently, fatigue was reported to be the greatest predictor of poor HRQOL in paediatric DMD. Understanding the trajectory of HRQOL and its relationship with fatigue may facilitate the development of improved therapeutic strategies. Our objective was to describe three-year changes in HRQOL and fatigue in children with DMD. Methods: Patients identified via the Canadian Neuromuscular Disease Registry received mailed questionnaires (2013–2016). HRQOL was assessed using the PedsQLTM GCS and NMM domains, and fatigue was assessed using the MFS domain (patient- and parent-report). Mean three-year change in scores were computed. Pearson correlations were computed between three-year change in HRQOL and fatigue. Results: Mean decline in MFS scores for patient- and parent-reports were 1.03 and 1.19, respectively. Mean decline in GCS scores for patient- and parent-report were 1.75 and 4.13, respectively. Mean change in NMM scores for patient- and parent-report were 0.72 and -8.36, respectively. Change in MFS score was associated with changes in GCS (r=0.72, p<0.001) and NMM scores (r=0.84, p<0.001) by patient-report. Conclusions: Children with DMD experience worse fatigue and HRQOL over time. Parents perceive a greater decline in HRQOL over time compared to patients.
To determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.
Individual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.
We searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.
Probiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25–0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23–0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11–4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89–1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89–1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.
Moderate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.