Large Particle Emissions from Human Vocalization and Playing of Wind Instruments.

Humans emit large salivary particles when talking, singing, and playing musical instruments, which have implications for respiratory disease transmission. Yet little work has been done to characterize the emission rates and size distributions of such particles. This work characterized large particle (dp > 35 µm in aerodynamic diameter) emissions from 70 volunteers of varying age and sex while vocalizing and playing wind instruments. Mitigation efficacies for face masks (while singing) and bell covers (while playing instruments) were also examined. Geometric mean particle count emission rates varied from 3.8 min-1 (geometric standard deviation [GSD] = 3.1) for brass instruments playing to 95.1 min-1 (GSD = 3.8) for talking. On average, talking produced the highest emission rates for large particles, in terms of both number and mass, followed by singing and then instrument playing. Neither age, sex, CO2 emissions, nor loudness (average dBA) were significant predictors of large particle emissions, contrary to previous findings for smaller particle sizes (i.e., for dp < 35 µm). Size distributions were similar between talking and singing (count median diameter = 53.0 µm, GSD = 1.69). Bell covers did not affect large particle emissions from most wind instruments, but face masks reduced large particle count emissions for singing by 92.5% (95% CI: 97.9%, 73.7%).

Understanding Parents' Experiences With Mainstream Schooling for Their Children With Autism Spectrum Disorder: A Meta-Analysis.

IMPORTANCE: Children with autism spectrum disorder (ASD) face school-related occupational challenges. Attending a mainstream school offers benefits for children's learning and their development of social skills; however, parents express frustration with ensuring their child's unique needs and preferences are met. OBJECTIVE: To gain insight into parents' experiences with the mainstream preschool and primary educational system for their children with ASD. DATA SOURCES: Eleven electronic databases were systematically searched, and processes were followed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. STUDY SELECTION AND DATA COLLECTION: Study eligibility was determined through the use of selection criteria and paired independent reviewers. Critical appraisal was conducted using a qualitative research hierarchy and a modified version of the Critical Appraisal Skills Programme tool. Two reviewers synthesized the data into themes, following the Joanna Briggs Institute meta-aggregation process. Twenty-six qualitative studies, representing the voices of 397 parents, are presented in this review (spanning 2013-2021). Articles were set in Westernized and non-Westernized settings and represented culturally and linguistically diverse population groups. FINDINGS: Parents of children with ASD reported a lack of awareness and understanding of their children's unique learning needs in the mainstream school system at all levels. CONCLUSIONS AND RELEVANCE: This review has various occupational therapy practice implications for supporting school-age children with ASD, their parents, and school staff. These include adopting family-centered and ecological approaches, raising awareness, influencing policy, and facilitating collaboration. What This Article Adds: This review provides guidance for occupational therapists working in schools about their practice in working at the individual, targeted, and whole-school levels to address occupational barriers faced by children with ASD.

Implementation and Mental Health Outcomes of a Service Cascade Linking Child Welfare and Children's Mental Health Systems: A Case Study of the Gateway CALL Demonstration.

The mental health needs of children and youth involved in the child welfare system remain largely unmet. Service cascades are an emerging approach to systematizing mental health screening, assessment, and treatment referral processes. However, evidence is minimal and inconsistent regarding the effectiveness of such approaches for improving mental health service access and outcomes. In an effort to address this gap, this study presents a case-study of the implementation fidelity and treatment outcomes of the Gateway CALL service cascade. Study analyses involved longitudinal data collected as part of a larger evaluation of Gateway CALL. Specifically, descriptive and linear mixed model analyses were conducted to assess the implementation of service cascade components, and changes in mental health outcomes (behavior problems) among 175 children placed out-of-home during the study. Study analyses found that although fidelity was strong early in the service cascade, implementation began to break down once components involved more than one service system (child welfare, mental health). However, results also indicated that parent-reported child behavior problems decreased significantly over time, despite later cascade components being implemented with poor fidelity to the Gateway CALL service model. For children and youth involved in child welfare systems, service cascades like Gateway CALL have the potential to significantly improve both mental health service receipt and outcomes. To maximize the effectiveness of such approaches, later phases of implementation may require increased attention and support, particularly regarding processes and outcomes that cross child welfare and mental health service systems.

Detection of SARS-CoV-2 in Neonatal Autopsy Tissues and Placenta.

Severe coronavirus disease in neonates is rare. We analyzed clinical, laboratory, and autopsy findings from a neonate in the United States who was delivered at 25 weeks of gestation and died 4 days after birth; the mother had asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and preeclampsia. We observed severe diffuse alveolar damage and localized SARS-CoV-2 by immunohistochemistry, in situ hybridization, and electron microscopy of the lungs of the neonate. We localized SARS-CoV-2 RNA in neonatal heart and liver vascular endothelium by using in situ hybridization and detected SARS-CoV-2 RNA in neonatal and placental tissues by using reverse transcription PCR. Subgenomic reverse transcription PCR suggested viral replication in lung/airway, heart, and liver. These findings indicate that in utero SARS-CoV-2 transmission contributed to this neonatal death.

Inflammatory Biomarkers and Intracranial Hemorrhage after Endovascular Thrombectomy.

BACKGROUND: Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage - more specifically, inflammatory biomarkers present in baseline serology. METHODS: We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor. RESULTS: Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage). CONCLUSION: Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.

Associations of warzone veteran mental health with partner mental health and family functioning: Family Foundations Study.

INTRODUCTION: Warzone participation is associated with increased risk of stress-related psychopathology, including posttraumatic stress disorder (PTSD) and depression. Prior research suggests that the mental health of spouses of warzone veterans (WZVs) is linked to that of their partners. Additionally, PTSD among WZVs has been associated with marital dysfunction. Less is known about the effects of depression among WZVs on partner mental health and family relationships. We sought in this study to examine associations between WZV PTSD and depression and partner mental health and relationship outcomes. METHODS: Using a nationally dispersed sample of Iraq and Afghanistan veterans and their married and unmarried intimate partners, 245 dyads completed structured psychiatric interviews and psychometric surveys assessing family functioning and relationship aggression. RESULTS: Adjusted regression analyses indicated that depression among WZVs was associated with partner depression and anxiety disorders. WZV PTSD and depression were also associated with partner-reported relationship dysfunction, dissatisfaction, and communication issues, and higher rates of intimate partner aggression victimization and perpetration. CONCLUSIONS: Mental health consequences of war extend beyond WZVs to the mental health of their intimate partners and their relationships with intimate partners.

Structural, Biochemical, and In Vivo Characterization of MtrR-Mediated Resistance to Innate Antimicrobials by the Human Pathogen Neisseria gonorrhoeae.

Neisseria gonorrhoeae responds to host-derived antimicrobials by inducing the expression of the mtrCDE-encoded multidrug efflux pump, which expels microbicides, such as bile salts, fatty acids, and multiple extrinsically administered drugs, from the cell. In the absence of these cytotoxins, the TetR family member MtrR represses the mtrCDE genes. Although antimicrobial-dependent derepression of mtrCDE is clear, the physiological inducers of MtrR are unknown. Here, we report the crystal structure of an induced form of MtrR. In the binding pocket of MtrR, we observed electron density that we hypothesized was N-cyclohexyl-3-aminopropanesulfonic acid (CAPS), a component of the crystallization reagent. Using the MtrR-CAPS structure as an inducer-bound template, we hypothesized that bile salts, which bear significant chemical resemblance to CAPS, are physiologically relevant inducers. Indeed, characterization of MtrR-chenodeoxycholate and MtrR-taurodeoxycholate interactions, both in vitro and in vivo, revealed that these bile salts, but not glyocholate or taurocholate, bind MtrR tightly and can act as bona fide inducers. Furthermore, two residues, W136 and R176, were shown to be important in binding chenodeoxycholate but not taurodeoxycholate, suggesting different binding modes of the bile salts. These data provide insight into a crucial mechanism utilized by the pathogen to overcome innate human defenses.IMPORTANCENeisseria gonorrhoeae causes a significant disease burden worldwide, and a meteoric rise in its multidrug resistance has reduced the efficacy of antibiotics previously or currently approved for therapy of gonorrheal infections. The multidrug efflux pump MtrCDE transports multiple drugs and host-derived antimicrobials from the bacterial cell and confers survival advantage on the pathogen within the host. Transcription of the pump is repressed by MtrR but relieved by the cytosolic influx of antimicrobials. Here, we describe the structure of induced MtrR and use this structure to identify bile salts as physiological inducers of MtrR. These findings provide a mechanistic basis for antimicrobial sensing and gonococcal protection by MtrR through the derepression of mtrCDE expression after exposure to intrinsic and clinically applied antimicrobials.

Family-specific Kinesin Structures Reveal Neck-linker Length Based on Initiation of the Coiled-coil.

Kinesin-1, -2, -5, and -7 generate processive hand-over-hand 8-nm steps to transport intracellular cargoes toward the microtubule plus end. This processive motility requires gating mechanisms to coordinate the mechanochemical cycles of the two motor heads to sustain the processive run. A key structural element believed to regulate the degree of processivity is the neck-linker, a short peptide of 12-18 residues, which connects the motor domain to its coiled-coil stalk. Although a shorter neck-linker has been correlated with longer run lengths, the structural data to support this hypothesis have been lacking. To test this hypothesis, seven kinesin structures were determined by x-ray crystallography. Each included the neck-linker motif, followed by helix α7 that constitutes the start of the coiled-coil stalk. In the majority of the structures, the neck-linker length differed from predictions because helix α7, which initiates the coiled-coil, started earlier in the sequence than predicted. A further examination of structures in the Protein Data Bank reveals that there is a great disparity between the predicted and observed starting residues. This suggests that an accurate prediction of the start of a coiled-coil is currently difficult to achieve. These results are significant because they now exclude simple comparisons between members of the kinesin superfamily and add a further layer of complexity when interpreting the results of mutagenesis or protein fusion. They also re-emphasize the need to consider factors beyond the kinesin neck-linker motif when attempting to understand how inter-head communication is tuned to achieve the degree of processivity required for cellular function.

Social inclusion for children with hearing loss in listening and spoken Language early intervention: an exploratory study.

BACKGROUND: Social inclusion is a common focus of listening and spoken language (LSL) early intervention for children with hearing loss. This exploratory study compared the social inclusion of young children with hearing loss educated using a listening and spoken language approach with population data. METHODS: A framework for understanding the scope of social inclusion is presented in the Background. This framework guided the use of a shortened, modified version of the Longitudinal Study of Australian Children (LSAC) to measure two of the five facets of social inclusion ('education' and 'interacting with society and fulfilling social goals'). The survey was completed by parents of children with hearing loss aged 4-5 years who were educated using a LSL approach (n = 78; 37% who responded). These responses were compared to those obtained for typical hearing children in the LSAC dataset (n = 3265). RESULTS: Analyses revealed that most children with hearing loss had comparable outcomes to those with typical hearing on the 'education' and 'interacting with society and fulfilling social roles' facets of social inclusion. CONCLUSIONS: These exploratory findings are positive and warrant further investigation across all five facets of the framework to identify which factors influence social inclusion.

Conformational activation of ADAMTS13.

A disintegrin and metalloprotease with thrombospondin motifs 13 (ADAMTS13) is a metalloprotease that regulates von Willebrand factor (VWF) function. ADAMTS13-mediated proteolysis is determined by conformational changes in VWF, but also may depend on its own conformational activation. Kinetic analysis of WT ADAMTS13 revealed ∼ 2.5-fold reduced activity compared with ADAMTS13 lacking its C-terminal tail (MDTCS) or its CUB1-2 domains (WTΔCUB1-2), suggesting that the CUB domains naturally limit ADAMTS13 function. Consistent with this suggestion, WT ADAMTS13 activity was enhanced ∼ 2.5-fold by preincubation with either an anti-CUB mAb (20E9) or VWF D4CK (the natural binding partner for the CUB domains). Furthermore, the isolated CUB1-2 domains not only bound MDTCS, but also inhibited activity by up to 2.5-fold. Interestingly, a gain-of-function (GoF) ADAMTS13 spacer domain variant (R568K/F592Y/R660K/Y661F/Y665F) was ∼ 2.5-fold more active than WT ADAMTS13, but could not be further activated by 20E9 mAb or VWF D4CK and was unable to bind or to be inhibited by the CUB1-2 domains, suggesting that the inhibitory effects of the CUB domains involve an interaction with the spacer domain that is disrupted in GoF ADAMTS13. Electron microscopy demonstrated a "closed" conformation of WT ADAMTS13 and suggested a more "open" conformation for GoF ADAMTS13. The cryptic spacer domain epitope revealed by conformational unfolding also represents the core antigenic target for autoantibodies in thrombotic thrombocytopenic purpura. We propose that ADAMTS13 circulates in a closed conformation, which is maintained by a CUB-spacer domain binding interaction. ADAMTS13 becomes conformationally activated on demand through interaction of its C-terminal CUB domains with VWF, making it susceptible to immune recognition.

Advanced Oxidation of Tartrazine and Brilliant Blue with Pulsed Ultraviolet Light Emitting Diodes.

This study investigated the effect of ultraviolet light-emitting diodes (UVLEDs) coupled with hydrogen peroxide as an advanced oxidation process (AOP) for the degradation of two test chemicals. Brilliant Blue FCF consistently exhibited greater degradation than tartrazine, with 83% degradation after 300 minutes at the 100% duty cycle compared with only 17% degradation of tartrazine under the same conditions. These differences are attributable to the structural properties of the compounds. Duty cycle was positively correlated with the first-order rate constants (k) for both chemicals but, interestingly, negatively correlated with the normalized first-order rate constants (k/duty cycle). Synergistic effects of both hydraulic mixing and LED duty cycle were manifested as novel oscillations in the effluent contaminant concentration. Further, LED output and efficiency were dependent upon duty cycle and less efficient over time perhaps due to heating effects on semiconductor performance.

Adsorption of Malathion onto Copper and Iron Surfaces Relevant to Water Infrastructure.

This study investigated the adsorption of malathion to copper and iron surfaces including microspheres and pipe specimens similar to those in drinking water infrastructure. The solid phase concentration of malathion on the virgin and used copper pipe specimens was generally between 0.2 - 1 mg/g. The adsorption capacity for copper and iron microspheres were greater than those of the pipe specimens because of their higher surface area-to-volume ratios. Copper materials adsorbed more malathion than comparable iron materials. XPS analysis of copper and iron surfaces revealed peaks at 164 eV (S 2p) and 135 eV (P 2p), which suggests that malathion chemically bonded to the surfaces of the specimens. Metal oxides likely formed stable bonds with phosphorus through pi conjugation. These findings are the first to show that malathion can chemically adhere to copper and iron pipe materials. This insight is critical for understanding the decontamination strategies needed for water networks.

Prenatal testosterone exposure decreases colocalization of insulin receptors in kisspeptin/neurokinin B/dynorphin and agouti-related peptide neurons of the adult ewe.

Insulin serves as a link between the metabolic and reproductive systems, communicating energy availability to the hypothalamus and enabling reproductive mechanisms. Adult Suffolk ewes prenatally exposed to testosterone (T) display an array of reproductive and metabolic dysfunctions similar to those seen in women with polycystic ovarian syndrome (PCOS), including insulin resistance. Moreover, prenatal T treatment alters neuropeptide expression in KNDy (co-expressing kisspeptin, neurokinin B/dynorphin) and agouti-related peptide (AgRP) neurons in the arcuate nucleus, two populations that play key roles in the control of reproduction and metabolism, respectively. In this study, we determined whether prenatal T treatment also altered insulin receptors in KNDy and AgRP neurons, as well as in preoptic area (POA) kisspeptin, pro-opiomelanocortin (POMC), and gonadotropin-releasing hormone (GnRH) neurons of the adult sheep brain. Immunofluorescent detection of the beta subunit of insulin receptor (IRß) revealed that KNDy, AgRP and POMC neurons, but not GnRH or POA kisspeptin neurons, colocalize IRß in control females. Moreover, prenatal T treatment decreased the percentage of KNDy and AgRP neurons that colocalized IRß, consistent with reduced insulin sensitivity. Administration of the anti-androgen drug, Flutamide, during prenatal T treatment, prevented the reduction in IRß colocalization in AgRP, but not in KNDy neurons, suggesting that these effects are programmed by androgenic and oestrogenic actions, respectively. These findings provide novel insight into the effects of prenatal T treatment on hypothalamic insulin sensitivity and raise the possibility that decreased insulin receptors, specifically within KNDy and AgRP neurons, may contribute to the PCOS-like phenotype of this animal model.

Wetland Soil Carbon in a Watershed Context for the Prairie Pothole Region.

Wetland restoration in the Prairie Pothole Region (PPR) often involves soil removal to enhance water storage volume and/or remove seedbanks of invasive species. Consequences of soil removal could include loss of soil organic carbon (SOC), which is important to ecosystem functions such as water-holding capacity and nutrient retention needed for plant re-establishment. We used watershed position and surface flow pathways to classify wetlands into headwater or network systems to address two questions relevant to carbon (C) cycling and wetland restoration practices: (i) Do SOC stocks and C mineralization rates vary with landscape position in the watershed (headwater vs. network systems) and land use (restored vs. native prairie grasslands)? (ii) How might soil removal affect plant emergence? We addressed these questions using wetlands at three large (?200 ha) study areas in the central North Dakota PPR. We found the cumulative amount of C mineralization over 90 d was 100% greater for network than headwater systems, but SOC stocks were similar, suggesting greater C inputs beneath wetlands connected by higher-order drainage lines are balanced by greater rates of C turnover. Land use significantly affected SOC, with greater stocks beneath native prairie than restored grasslands for both watershed positions. Removal of mineral soil negatively affected plant emergence. This watershed-based framework can be applied to guide restoration designs by (i) weighting wetlands based on surface flow connectivity and contributing area and (ii) mapping the effects of soil removal on plant and soil properties for network and headwater wetland systems in the PPR.

Nitrous Oxide Fluxes, Soil Oxygen, and Denitrification Potential of Urine- and Non-Urine-Treated Soil under Different Irrigation Frequencies.

Despite increased use of irrigation to improve forage quality and quantity for grazing cattle ( Linnaeus), there is a lack of data that assess how irrigation practices influence nitrous oxide (NO) emissions from urine-affected soils. Irrigation effects on soil oxygen (O) availability, a primary controller of NO fluxes, is poorly understood. It was hypothesized that increased irrigation frequency would result in lower NO emissions by increasing soil moisture and decreasing soil O concentrations. This would favor more NO reduction to dinitrogen (N). We examined effects of high (3-d) versus low (6-d) irrigation frequency with and without bovine urine addition to pasture. Nitrous oxide fluxes were measured daily for 35 d. Soil O, temperature, and water content were continuously measured at multiple depths. Inorganic nitrogen, organic carbon, and soil pH were measured at 6-d intervals. Measurements of denitrification enzyme activity with and without acetylene inhibition were used to infer the NO/(NO + N) ratio. The NO/(NO + N) ratio was lower under high- compared with low-frequency irrigation, suggesting greater potential for NO reduction to N with more frequent irrigation. Although NO fluxes were increased by urine addition, they were not affected by irrigation frequency. Soil O decreased temporarily after urine deposition, but O dynamics did not explain NO dynamics. Relative soil gas diffusivity (/) was a better predictor of NO fluxes than O concentration. On a free-draining soil, increasing irrigation frequency while providing the same total water volume did not enhance NO emissions under ruminant urine patches in a grazed pasture.

The effect of malathion on the activity, performance, and microbial ecology of activated sludge.

This study evaluated the effect of a VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate) surrogate (malathion) on the activity, performance, and ecology of activated sludge bioreactors. In the presence of malathion, the maximum observed respiration rates varied between 43 and 53 µg/O2 min, generally similar to the 49 µg O2/min rates observed in controls. Malathion did not alter the respiration ratio of O2 consumed-to-CO2 produced nor did it impact the shape of the oxygen consumption curves during respirometry. Shorter term (12 h) batch tests showed that both chemical oxygen demand (COD) and ammonia removal were not negatively impacted by the presence of 0.1-3 mg/L malathion. Longer term continuous addition (i.e. 40 days) of 0.1 mg/L of malathion also had no effect on COD and ammonia removal. In contrast to shorter term exposures, longer term continuous addition of 3 mg/L of malathion negatively impacted both COD and nitrogen removal and was associated with shifts in the abundance of species that are common to activated sludge. These results illustrate the impact that chemicals like malathion may have on COD removal, and nitrification, as well as the robustness of activated sludge microbial communities.

HYPERSPECTRAL ANALYSIS FOR STANDOFF DETECTION OF DIMETHYL METHYLPHOSPHONATE ON BUILDING MATERIALS.

Detecting organophosphates in indoor settings can greatly benefit from more efficient and faster methods of surveying large surface areas than conventional approaches, which sample small surface areas followed by extraction and analysis. This study examined a standoff detection technique utilizing hyperspectral imaging for analysis of building materials in near-real time. In this proof-of-concept study, dimethyl methylphosphonate (DMMP) was applied to stainless steel and laminate coupons and spectra were collected during active illumination. Absorbance bands at approximately 1275 cm-1 and 1050 cm-1 were associated with phosphorus-oxygen double bond (P=O) and phosphorus-oxygen-carbon (P-O-C) bond stretches of DMMP, respectively. The magnitude of these bands increased linearly (r2 = 0.93) with DMMP across the full absorbance spectrum, between ν1 = 877 cm-1 to ν2 = 1262 cm-1. Comparisons between bare and contaminated surfaces on stainless steel using the spectral contrast angle technique indicated that the bare samples showed no sign of contamination, with large uniformly distributed contrast angles of 45°-55°, while the contaminated samples had smaller spectral contact angles of < 20° in the contaminated region and > 40° in the uncontaminated region. The laminate contaminated region exhibited contact angles of < 25°. To the best of our knowledge, this is the first report to demonstrate that hyperspectral imaging can be used to detect DMMP on building materials, with detection levels similar to concentrations expected for some organophosphate deposition scenarios.

Does mothers' postnatal depression influence the development of imitation?

BACKGROUND: Links between mothers' postnatal depression (PND) and children's cognition have been identified in several samples, but the evidence is inconsistent. We hypothesized that PND may specifically interfere with infants' imitation, an early learning ability that features in early mother-infant interaction and is linked to memory, causal understanding and joint attention. METHODS: A randomly controlled experiment on imitation was embedded into a longitudinal study of a representative sample of firstborn British infants, whose mothers were assessed for depression using the SCAN interview during pregnancy and at 6 months postpartum. At a mean of 12.8 months, 253 infants were presented with two imitation tasks that varied in difficulty, in counterbalanced order. RESULTS: The infants of mothers who experienced PND were significantly less likely than other infants in the sample to imitate the modelled actions, showing a 72% reduction in the likelihood of imitation. The association with PND was not explained by sociodemographic adversity, or a history of depression during pregnancy or prior to conception. Mothers' references to infants' internal states during mother-infant interaction at 6 months facilitated imitation at 12 months, but did not explain the link with PND. CONCLUSIONS: The findings support the hypothesis that associations between PND and later cognitive outcomes may partly derive from effects of the mother's illness on infants' early learning abilities. Support for infants' learning should be considered as an age-appropriate, child-focused component of interventions designed to ameliorate the effects of PND.

Citrate salts for preventing and treating calcium containing kidney stones in adults.

BACKGROUND: Kidney stones affect people worldwide and have a high rate of recurrence even with treatment. Recurrences are particularly prevalent in people with low urinary citrate levels. These people have a higher incidence of calcium phosphate and calcium oxalate stones. Oral citrate therapy increases the urinary citrate levels, which in turn binds with calcium and inhibits the crystallisation thus reduces stone formation. Despite the widespread use of oral citrate therapy for prevention and treatment of calcium oxalate stones, the evidence to support its clinical efficacy remains uncertain. OBJECTIVES: The objective of this review was to determine the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 29 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed the efficacy and adverse events associated with citrate salts for the treatment and prevention of calcium containing kidney stones in adults treated for a minimum of six months. DATA COLLECTION AND ANALYSIS: Two authors assessed studies for inclusion in this review. Data were extracted according to predetermined criteria. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. MAIN RESULTS: We included seven studies that included a total of 477 participants, most of whom had oxalate stones. Of these, three studies (247 participants) compared potassium citrate with placebo or no intervention; three (166 participants) compared potassium-sodium citrate with no intervention; and one (64 participants) compared potassium-magnesium citrate with placebo. Overall, quality of the reporting of the included studies was considered moderate to poor, and there was a high risk of attrition bias in two studies.Compared with placebo or no intervention, citrate therapy significantly reduced the stone size (4 studies, 160 participants: RR 2.35, 95% CI 1.36 to 4.05). New stone formation was significantly lower with citrate therapy compared to control (7 studies, 324 participants: RR 0.26, 95% CI 0.10 to 0.68). The beneficial effect on stone size stability was also evident (4 studies, 160 participants: RR 1.97, 95% CI 1.19 to 3.26). Adverse events were reported in four studies, with the main side effects being upper gastrointestinal disturbance and one patient reported a rash. There were more gastrointestinal adverse events in the citrate group; however this was not significant (4 studies, 271 participants: RR 2.55, 95% CI 0.71 to 9.16). There were significantly more dropouts due to adverse events with citrate therapy compared to control (4 studies, 271 participants: RR 4.45, 95% CI 1.28 to 15.50). The need for retreatment was significantly less with citrate therapy compared to control (2 studies, 157 participants: RR 0.22, 95% CI 0.06 to 0.89). AUTHORS' CONCLUSIONS: Citrate salts prevent new stone formation and reduce further stone growth in patients with residual stones that predominantly contain oxalate. The quality of reported literature remains moderate to poor; hence a well-designed statistically powered multi-centre RCT is needed in order to answer relevant questions concerning the efficacy of citrate salts.

Achieving patient-centred care: the potential and challenge of the patient-as-professional role.

BACKGROUND: The patient-as-professional concept acknowledges the expert participation of patients in interprofessional teams, including their contributions to managing and coordinating their care. However, little is known about experiences and perspectives of these teams. OBJECTIVE: To investigate (i) patients' and carers' experiences of actively engaging in interprofessional care by enacting the patient-as-professional role and (ii) clinicians' perspectives of this involvement. DESIGN, SETTING AND PARTICIPANTS: A two-phased qualitative study. In Phase 1, people with chronic disease (n = 50) and their carers (n = 5) participated in interviews and focus groups. Phase 2 involved interviews with clinicians (n = 14). Data were analysed thematically. FINDINGS: Patients and carers described the characteristics of the role (knowing about the condition, questioning clinicians, coordinating care, using a support network, engaging an advocate and being proactive), as well as factors that influence its performance (the patient-clinician partnership, benefits, barriers and applicability). However, both patients and carers, and clinicians cautioned that not all patients might desire this level of involvement. Clinicians were also concerned that not all patients have the required knowledge for this role, and those who do are time-consuming. When describing the inclusion of the patient-as-professional, clinicians highlighted the patient and clinician's roles, the importance of the clinician-patient relationship and ramifications of the role. CONCLUSION: Support exists for the patient-as-professional role. The characteristics and influencing factors identified in this study could guide patient engagement with the interprofessional team and support clinicians to provide patient-centred care. Recognition of the role has the potential to improve health-care delivery by promoting patient-centred care.