Mental state verb use in play by preschool-age children who stutter and their mothers.

INTRODUCTION: Preschool-age children use mental state verbs (MSVs; e.g., think, know) to reference thoughts and other cognitive states. In play-based language, MSV use requires conversational flexibility, as speakers shift from discussion of actions happening in the here-and-now to more abstract discussion of mental states. Some evidence suggests that children who stutter (CWS) demonstrate subtle differences in shifting on experimental tasks of cognitive flexibility, differences which may extend to conversational flexibility. This study explored MSV use in conversational language between CWS and their mothers. METHODS: Thirty-five preschool-age CWS and 35 age- and gender-matched children who do not stutter (CWNS), all performing within the typical range on standardized language testing, conversed with their mothers during play. Samples were transcribed and coded for MSV use. RESULTS: No between-group differences were observed in MSV use, either between the CWS and CWNS or between the groups of mothers. Age and language skills were positively associated with MSV use in the CWNS group only. For both groups of dyads, mothers' MSV use corresponded at least to some extent to their children's language skills. Finally, correspondence between CWNS and their mothers was observed for two conversational language measures, representing lexical diversity and morphosyntax; this overall pattern was not observed in the CWS dyad group. CONCLUSIONS: Although these findings point to similar use of MSVs among the groups of children and their mothers, for the CWS group, the patterns of use in relation to age and language skills are somewhat different from developmental expectations.

Why surveys are 'very hard': exploring challenges and insights for collection of authentic patient experience information with speakers of Australian First Nations languages.

INTRODUCTION: Health services collect patient experience data to monitor, evaluate and improve services and subsequently health outcomes. Obtaining authentic patient experience information to inform improvements relies on the quality of data collection processes and the responsiveness of these processes to the cultural and linguistic needs of diverse populations. This study explores the challenges and considerations in collecting authentic patient experience information through survey methods with Australians who primarily speak First Nations languages. METHODS: First Nations language experts, interpreters, health staff and researchers with expertise in intercultural communication engaged in an iterative process of critical review of two survey tools using qualitative methods. These included a collaborative process of repeated translation and back translation of survey items and collaborative analysis of video-recorded trial administration of surveys with languages experts (who were also receiving dialysis treatment) and survey administrators. All research activities were audio- or video-recorded, and data from all sources were translated, transcribed and inductively analysed to identify key elements influencing acceptability and relevance of both survey process and items as well as translatability. RESULTS: Serious challenges in achieving equivalence of meaning between English and translated versions of survey items were pervasive. Translatability of original survey items was extensively compromised by the use of metaphors specific to the cultural context within which surveys were developed, English words that are familiar but used with different meaning, English terms with no equivalent in First Nations languages and grammatical discordance between languages. Discordance between survey methods and First Nations cultural protocols and preferences for seeking and sharing information was also important: the lack of opportunity to share the 'full story', discomfort with direct questions and communication protocols that preclude negative or critical responses constrained the authenticity of the information obtained through survey methods. These limitations have serious implications for the quality of information collected and result in frustration and distress for those engaging with the survey. CONCLUSION: Profound implications for the acceptability of a survey tool as well as data quality arise from differences between First Nations cultural and communication contexts and the cultural context within which survey methods have evolved. When data collection processes are not linguistically and culturally congruent there is a risk that patient experience data are inaccurate, miss what is important to First Nations patients and have limited utility for informing relevant healthcare improvement. Engagement of First Nations cultural and language experts is essential in all stages of development, implementation and evaluation of culturally safe and effective approaches to support speakers of First Nations languages to share their experiences of health care and influence change.

Need for cardiac implantable electronic devices and long-term follow-up in recipients of orthotopic heart transplants.

BACKGROUND: Cardiac pacemaker implantation after orthotopic heart transplantation declined dramatically after development of the bicaval anastomosis technique. However, much less is known about the rate, indications, and predictors of device implantation procedures with the current surgical technique. OBJECTIVE: The purpose of this study was to evaluate the indications, patient characteristics, incidence, and survival related to cardiac implantable electronic device (CIED) implantation after heart transplantation. METHODS: This was a single-center study of 399 consecutive adult recipients of orthotopic heart transplants with bicaval anastomosis from 1991 to 2017. The primary end point was freedom from pacemaker or implantable cardioverter-defibrillator (ICD) implantation, and the secondary end point was all-cause mortality. RESULTS: At the time of transplantation, the mean age of recipients was 50 ± 12 years and that of donors 31 ± 12 years. CIEDs were implanted in 8% of recipients (n = 31): 11 pacemakers (35%) for sinus node dysfunction, 17 (55%) for high-grade heart block, and 3 ICDs (10%) for the primary prevention of sudden cardiac death. Early CIED implantation (<30 days) was rare and absent for sinus node dysfunction. The risk for CIED implantation increased progressively during follow-up (0-30 years; median 11 years), with low-, moderate-, and high-risk periods between 0 and 10, between 10 and 20, and between 20 and 30 years, respectively. Recipients receiving CIEDs survived longer after transplantation (21 years vs 13 years; P < .01). Recipients receiving pacemakers for heart block were more likely to receive older donor hearts at the time of transplantation. CONCLUSION: The risk of pacemaker implantation increases progressively, while ICD implantation is rare. Donor age is the predominant risk factor for subsequent heart block. Early sinus node dysfunction requiring permanent pacing is rare.

Texture and flavor evaluation of peanut butter stabilized with natural waxes.

Natural peanut butter was stabilized with 1.0%-2.0% (w/w) beeswax (BW), candelilla wax (CLW), rice bran wax (RBW), or sunflower wax (SFW). The appearance, spreadability, mouthfeel, and flavor attributes of these samples were evaluated by a trained sensory panel using commercial stabilized peanut butter and a sample stabilized with hydrogenated cottonseed oil as references. The waxes and their blend ratio significantly (p < 0.05) influenced appearance, spreadability, firmness, mouthfeel, and flavor attributes. Samples with 1.5%-2.0% CLW, or 1.0%-1.5% RBW had the fewest differences in appearance and texture from the reference and commercial samples. However, an off-flavor was attributed to 1.5% or higher CLW. Samples stabilized with BW or with 1.0%-1.5% RBW had the fewest difference in flavor compared to the reference sample. Overall, samples stabilized with 1.0%-1.5% RBW scored closest to the commercial and reference samples. The response of CLW, RBW, and SFW (which was only evaluated for appearance and spreadability) indicates that amounts of these waxes could be tailored in different products to achieve a product with desirable texture and flavor as well as stability to oil loss. PRACTICAL APPLICATION: This research provides information that could be used by food companies that make seed or nut butters as spreads or as ingredients for use in foods. It shows the impact of the use of four types of waxes as stabilizers, at commercially relevant levels (< 3.0%), and at levels previously shown to be effective for stabilization, on the firmness, spreadability, and other texture and flavor attributes, and thus provides a starting point for optimization for commercial product specifications.

Perceived impact of formulating, implementing and enacting national mental health policies recommendations in practice: An exploratory qualitative study within child and adolescent mental health services in Scotland.

OBJECTIVE: To understand the process of formulating, implementing and enacting national recommendations into practice, by exploring the interactions between government policymakers and national and local organisations supporting and delivering policy implementation within a Child and Adolescent Mental Health Service (CAMHS) context in Scotland. METHODS: Data collection involved 16 semi-structured individual and four focus group interviews with a purposeful sample of policymakers, national health and social care stakeholders and local outpatient and inpatient CAMHS teams representing three NHS health boards in Scotland. RESULTS: Study participants highlighted the challenges of navigating through evolving and often conflicting policy agendas, seen to not acknowledging the current evidence base or experiential learning from services and prior evaluations. Accounts of transformation fatigue often emerged from increased expectations for staff to adopt new approaches to accommodate constantly changing recommendations. Participants also reported a lack of integration and implementation support from national health and social care organisations, leading to duplication of effort and gaps in provision or waste. Policy recommendations were perceived as sometimes vague, lacking clarity about how to deliver service transformation using a whole-system approach. The collective narratives reflected increased tension between the need for local autonomy to innovate and the limitations created vertically by the relative inflexibility of policy recommendations, and horizontally by the proliferation of national organisations delivering the same transformation aims using different approaches in a resource-constrained environment. CONCLUSION: The findings contribute to the wider literature by offering an exploration of importance of evaluation and evidence uptake in policy formulation; the roles and remits in supporting the implementation of policy recommendations; and how the dynamics of central control and local autonomy might impact on the local enactment of policy recommendations.

The impact of the United Nations Convention on the Rights of Persons with Disabilities (CRPD) on Victorian guardianship practice.

PURPOSE: Article 12 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD) emphasises full and equal legal capacity of all citizens to participate in decisions. This paper examines whether the principles of Article 12, also reflected in other reform documents, were evident within 12 guardianship hearings conducted in Victoria, Australia from 2001 to 2016 involving adults with cognitive disability. The issues this study raises resonate loudly across the globe as multiple signatory nations to the CRPD grapple with the complexities of implementing Article 12. METHODS: Reports of VCAT decisions with written reasons of Guardianship List hearings from 2001 to 2016 were selected from the Australasian Legal Information Institute site and analysed thematically. RESULTS: Thematic analysis of proceedings revealed three consistent trends. Firstly, a presumption of incapacity based on disability excluded Proposed Represented Persons (PRP) from involvement in decision-making. Secondly, external perceptions of PRPs best interest were dominated by safeguarding concerns and conflict between supporters. Finally, in multiple cases, although a PRP's preference had been established, it was considered immaterial to the final decision. CONCLUSIONS: The paper concludes with a promising discussion of the new Guardianship and Administration Act 2019 (Vic), which came into force on 1 March 2020, and recommendations for guardianship practice both locally and internationally.IMPLICATIONS FOR REHABILITATIONLegal capacity should be recognised as inherent in all people, and therefore decision making incapacity should not be assumed based on a person's cognitive and/or communication disability;The supported decision making mechanisms, born from Article 12 of the CRPD, that facilitate acknowledgment, interpretation and acting upon a person's expression of will and preference need to be recognised and promoted within the context of Guardianship proceedings and by health professionals when assessing decision making capacity of people with cognitive disability;Significant knowledge and attitudinal changes are required within the Tribunal and incorporated into the practice of health professionals informing the Tribunal, in order to counter many conceptual underpinnings embedded within current guardianship legislation across the globe;Ascertaining the will and preference of the proposed represented person should be prioritised by Guardianship tribunal members' rather than the management of conflict between interested parties.

"It was one of those complicated cases": health practitioners' perspectives and practices of providing end-of-life care for people with profound intellectual and multiple disability.

BACKGROUND: Due to developments in health and social care, people with profound intellectual and multiple disability (PIMD) are living longer than ever before, meaning they are increasingly experiencing life-threatening health conditions requiring palliative care. Little is known about providing end-of-life care for people with PIMD. The aim of this study was to explore health practitioners' perspectives and practices relating to end-of-life decision-making and planning for people with PIMD. METHODS: Seven in-depth semi-structured interviews were conducted with health practitioners employed in a range of hospital and community services throughout Melbourne, Australia. Questions were designed to gather information about their experience, perceptions, and attitudes relating to people with PIMD during and at the end of their life. Each interview, ranging from 40 to 60 min in length, was audio recorded and transcribed. Inductive thematic analysis was used to analyse the data. RESULTS: Four main themes emerged: limited participation, bias, dignity, and quality of death. Health practitioners indicated that people with PIMD are frequently excluded from participating in decision-making related to end-of-life care. Participants discussed reasons for this exclusion including challenges with communication and cognition. Participants reported a need for additional support and guidance in providing care for people with PIMD at the end of life. Professional and family bias played a role in end-of-life decision-making for people with PIMD. Participants reported a disproportional focus by palliative care practitioners on physical as opposed to emotional and spiritual well-being for patients with PIMD at the end of life. Finally, participants reported that people with PIMD generally did not die in specialised palliative care settings, but in segregated supported living environments. CONCLUSIONS: Due to negative perceptions of a person with PIMD's decision-making capacity, people with PIMD are likely to be assessed as unable to express choice and preference regarding end-of-life care and are offered limited opportunity to be involved in their own end-of-life care. This research provides guidance for the development of training and professional development relating to people with PIMD at the end of life. It is hoped that this will increase the accessibility of end-of-life services for people with PIMD, ensuring that a respectful and dignified death can be a reality for all humankind regardless of disability.

Prioritization of Pesticides for Assessment of Risk to Aquatic Ecosystems in Canada and Identification of Knowledge Gaps.

Pesticides can enter aquatic environments via direct application, via overspray or drift during application, or by runoff or leaching from fields during rain events, where they can have unintended effects on non-target aquatic biota. As such, Fisheries and Oceans Canada identified a need to prioritize current-use pesticides based on potential risks towards fish, their prey species, and habitats in Canada. A literature review was conducted to: (1) Identify current-use pesticides of concern for Canadian marine and freshwater environments based on use and environmental presence in Canada, (2) Outline current knowledge on the biological effects of the pesticides of concern, and (3) Identify general data gaps specific to biological effects of pesticides on aquatic species. Prioritization was based upon recent sales data, measured concentrations in Canadian aquatic environments between 2000 and 2020, and inherent toxicity as represented by aquatic guideline values. Prioritization identified 55 pesticides for further research nationally. Based on rank, a sub-group of seven were chosen as the top-priority pesticides, including three herbicides (atrazine, diquat, and S-metolachlor), three insecticides (chlorpyrifos, clothianidin, and permethrin), and one fungicide (chlorothalonil). A number of knowledge gaps became apparent through this process, including gaps in our understanding of sub-lethal toxicity, environmental fate, species sensitivity distributions, and/or surface water concentrations for each of the active ingredients reviewed. More generally, we identified a need for more baseline fish and fish habitat data, ongoing environmental monitoring, development of marine and sediment-toxicity benchmarks, improved study design including sufficiently low method detection limits, and collaboration around accessible data reporting and management.

Complex nonverbal response inhibition and stopping impulsivity in childhood stuttering.

PURPOSE: The primary purpose of this study was to examine complex nonverbal response inhibition and stopping impulsivity in children who do (CWS) and do not stutter (CWNS). METHOD: A total of 30 CWS and 30 CWNS between the ages of 3;1 and 6;0 (years; months) performed the Peg-Tapping Task (PTT; Diamond & Taylor, 1996; Luria, 1966), in which children were required to tap a dowel once when an examiner taps twice and vice versa. The main dependent variables were the number of practice trials, response accuracy, response latency for accurate responses, and the number of extra taps (i.e., tapping more than two times). RESULTS: The CWS were less accurate and slower on the PTT than the CWNS, with no differences in the number of practice trials. Furthermore, the CWS, especially boys, produced more extra taps than the CWNS. CONCLUSIONS: Findings revealed that preschool CWS have weaknesses in complex response inhibition and stopping impulsivity in the nonverbal domain compared to CWNS. Taken together, these findings along with those of previous studies indicate that CWS may have weaknesses in inhibition and impulsivity in the nonverbal domain as well as the verbal domain, suggesting a domain-general weakness.

Acute fetal response to high-intensity interval training in the second and third trimesters of pregnancy.

The majority of women do not meet the recommended levels of exercise during their pregnancies, frequently due to a lack of time. High-intensity interval training offers a potential solution, providing an effective, time-efficient exercise modality. This exercise modality has not been studied in pregnancy therefore, the objective of this study was to evaluate fetal response to a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy. Fourteen active, healthy women with uncomplicated, singleton pregnancies participated in a high-intensity interval training resistance circuit between 28 + 0/7 and 32 + 0/7 weeks. A Borg rating of perceived exertion of 15-17/20 and an estimated heart rate of 80%-90% of maternal heart-rate maximum was targeted. Fetal well-being was evaluated continuously with fetal heart-rate tracings and umbilical artery Doppler velocimetry conducted pre-and post-exercise. Fetal heart rate tracings were normal throughout the exercise circuit. Post-exercise, umbilical artery end-diastolic flow was normal and significant decreases were observed in the mean systolic/diastolic ratios, pulsatility indexes and resistance indexes. Therefore, in a small cohort of active pregnant women, a high-intensity interval training resistance circuit in the late second and early third trimesters of pregnancy appears to be a safe exercise modality with no acute, adverse fetal effects but further study is required. Novelty: High-intensity interval training, at an intensity in excess of current recommendations, does not appear to be associated with any adverse fetal effects in previously active pregnant women. High-intensity interval training is an enjoyable and effective exercise modality in previously active pregnant women.

Challenging the obesity paradox: extreme obesity and COPD mortality in the SUMMIT trial.

Populations with COPD demonstrate higher survival in overweight and obese compared with normal weight; the "obesity paradox". Relationships in less-severe COPD are unclear, as is the impact of cardiovascular risk, and few studies include individuals at extremes of obesity. We examined the relationship between body mass index (BMI; defined as underweight: <20 kg·m-2, normal: 20-25 kg·m-2, overweight: 25- <30 kg·m-2, obese class I: 30- <35 kg·m-2, class II: 35- <40 kg·m-2 and class III: ≥40 kg·m-2), morbidity, and mortality in the SUMMIT trial population (n=16 485), characterised by moderate COPD and heightened cardiovascular risk with a substantial proportion with class III obesity. The association between BMI category and time to event was modelled via proportional hazards (reference normal weight) adjusted for demographics and cardiorespiratory disease. Consistent with the paradox, underweight individuals demonstrated higher mortality (hazard ratio (HR) 1.31 (95% CI 1.04-1.64)), with lower mortality among overweight (HR 0.62 (95% CI 0.52-0.73)) and obese class I (HR 0.75 (95% CI 0.62-0.90)). However, mortality increased in obese class III (HR 1.36 (95% CI 1.00-1.86)). Death was primarily attributable to cardiovascular causes. Within a large, multinational cohort with moderate COPD and increased cardiovascular risk, the phenomenon of reduced mortality with obesity did not persist at BMI >40 kg·m-2, suggesting that obesity may not remain protective at the extremes in this population.

Multiecho complex total field inversion method (mcTFI) for improved signal modeling in quantitative susceptibility mapping.

PURPOSE: Typical quantitative susceptibility mapping (QSM) reconstruction steps consist of first estimating the magnetization field from the gradient-echo images, and then reconstructing the susceptibility map from the estimated field. The errors from the field-estimation steps may propagate into the final QSM map, and the noise in the estimated field map may no longer be zero-mean Gaussian noise, thus, causing streaking artifacts in the resulting QSM. A multiecho complex total field inversion (mcTFI) method was developed to compute the susceptibility map directly from the multiecho gradient echo images using an improved signal model that retains the Gaussian noise property in the complex domain. It showed improvements in QSM reconstruction over the conventional field-to-source inversion. METHODS: The proposed mcTFI method was compared with the nonlinear total field inversion (nTFI) method in a numerical brain with hemorrhage and calcification, the numerical brains provided by the QSM Challenge 2.0, 18 brains with intracerebral hemorrhage scanned at 3T, and 6 healthy brains scanned at 7T. RESULTS: Compared with nTFI, the proposed mcTFI showed more accurate QSM reconstruction around the lesions in the numerical simulations. The mcTFI reconstructed QSM also showed the best image quality with the least artifacts in the brains with intracerebral hemorrhage scanned at 3T and healthy brains scanned at 7T. CONCLUSION: The proposed multiecho complex total field inversion improved QSM reconstruction over traditional field-to-source inversion through better signal modeling.

Testing and implementing video consulting for outpatient appointments: using quality improvement system thinking and codesign principles.

Increasing demand for outpatient appointments (OPA) is a global challenge for healthcare providers. Non-attendance rates are high, not least because of the challenges of attending hospital OPAs due to transport difficulties, cost, poor health, caring and work responsibilities. Digital solutions may help ameliorate these challenges. This project aimed to implement codesigned outpatient video consultations across National Health Service (NHS) Highland using system-wide quality improvement approaches to implementation, involving patients, carers, clinical and non-clinical staff, national and local strategic leads. System mapping; an intensive codesign process involving extensive stakeholder engagement and real-time testing; Plan, Do, Study, Act cycles; and collection of clinician and patient feedback were used to optimise the service. Standardised processes were developed and implemented, which made video consulting easy to use for patients, embedded video into routine health service systems for clinicians and non-clinical staff, and automated much of the administrative burden. All clinicians and staff are using the system and both groups identified benefits in terms of travel time and costs saved. Transferable lessons for other services are identified, providing a practical blueprint for others to adapt and use in their own contexts to help implement and sustain video consultation services now and in the future.

A comparison of the performance of Persian speaking children who do and do not stutter on three nonwords repetition tasks.

PURPOSE: The purpose of the study was to examine the performance of Persian speaking children who stutter (CWS) and children who do not stutter (CWNS) on three nonword repetition tasks, while also focusing on which task and scoring method best differentiates the two groups of children. METHOD: Thirty CWS and 30 CWNS between the ages of 5;0 to 6;6 completed three nonword repetition tasks that varied in complexity. Each task was scored using two methods: nonwords correct and phonemes correct. Between-group differences in performance on each task were examined, along with disfluencies for CWS and the task and scoring method that best differentiated the CWS and CWNS. RESULTS: The findings revealed that, across all three nonword repetition tasks, the CWS consistently produced fewer nonwords correct and phonemes correct than the CWNS group at virtually all syllable lengths. The CWS produced more disfluencies on longer nonwords than shorter nonwords in all three nonword repetition tasks. The nonword repetition task with lower wordlikeness and more phonologically complex items best differentiated the two groups of children. Findings further revealed that discriminative accuracy was highest for scoring based on the number of phonemes produced correctly. CONCLUSION: Findings provide further evidence to suggest that CWS may have difficulty with phonological working memory and/or phonological processing.

Targeted Endodontic Microsurgery: Implications of the Greater Palatine Artery.

INTRODUCTION: Targeted Endodontic Microsurgery (TEMS) combines trephine burs and 3D-printed guides to make flapless maxillary palatal root-end surgery possible. This study assessed the location of the greater palatine artery (GPA), the relationship of the GPA to maxillary molar root ends, and the feasibility of flapless palatal-approach TEMS. METHODS: Three endodontists analyzed 250 cone-beam computed tomographic images of maxillary molars for (1) transition morphology between the hard palate and the alveolar process adjacent to first and second molars as an indication of the most likely location of the GPA, (2) the superior-inferior relationship between the GPA and root ends, and (3) the feasibility of palatal-approach TEMS. RESULTS: Palatal transition morphology included 20% Spine, 72% Bridge, and 8% Smooth. GPA position as related to palatal root ends was classified as 34% superior, 40% adjacent, and 21% inferior. Five percent of classifications were undefined. TEMS was deemed feasible for 47% of maxillary first molars and 52% of second molars, and was significantly more feasible with GPAs superior to palatal root ends. Reasons for infeasibility included GPA proximity and unfavorable resection angle or level. Maxillary first molar palatal roots were 11.13 ± 2.68 mm from the greater palatine foramen (GPF) and 2.37 ± 1.46 mm from the GPA. Second molar palatal roots were 4.94 ± 2.55 mm from the GPF and 2.53 ± 1.77 mm from the GPA. CONCLUSIONS: Palatal transition morphology and GPA position adjacent to maxillary molars, as manifested in cone-beam computed tomographic coronal views, suggested maxillary palatal root TEMS could be accomplished with a 2-mm safety margin in 47% of first molars and 52% of second molars. Historical paradigms that do not consider flapless palatal surgical approaches may need to be revised.

Chronic toxicity of technical atrazine to the fathead minnow (Pimephales promelas) during a full life-cycle exposure and an evaluation of the consistency of responses.

Fathead minnows (Pimephales promelas) were continuously exposed to the herbicide atrazine (0.15, 0.25, 0.46, 0.99, and 2.0 mg a.i./L, plus dilution water and solvent controls) for a complete life cycle (274 days). Concentrations of atrazine up to 2.0 mg a.i./L did not significantly reduce hatching success, larval survival at 30 or 60 days post-hatch, or reproduction (eggs/spawn, total eggs, spawns/female, or eggs/female) in the F0 generation. However, at 60 days of exposure, total length and total survival to study completion were significantly reduced in ≥0.46 mg a.i./L and ≥ 0.99 mg a.i./L treatments, respectively. In the F1 generation, hatchability of embryos at ≥0.25 mg a.i./L (range 74-82%) was significantly less than that of pooled control organisms (86%). Following 30 days' post-hatch exposure, F1 survival was not significantly different from pooled control for any treatment. Finally, tissues representing major life stages had bioconcentration factors ranging from 3.7× (F1 embryos, <24 h) to 8.5× (F0 adults), indicating little to no evidence of bioconcentration. We developed a series of questions to assess the consistency of observed responses in order to place the data in context with the wider available and relevant literature (e.g., Observed between studies? Observed between species? Observed at lower levels of biological organization?). The analysis for consistency supports the conclusion that atrazine does not pose a significant chronic risk to freshwater fish in terms of growth, reproduction, or survivorship at concentrations of up to at least 100 µg/L.

Pharmacotherapy and Lung Function Decline in Patients with Chronic Obstructive Pulmonary Disease. A Systematic Review.

Rationale: Whether pharmacological therapy alters decline in FEV1 in chronic obstructive pulmonary disease remains controversial. Because pharmacotherapy improves health status, exacerbation rate, and symptoms, it may be unethical to complete placebo-controlled long-term studies aimed at modifying FEV1 decline.Objectives: We conducted a systematic review of placebo-controlled pharmacological trials lasting ≥1 year to address the question of whether therapy alters FEV1 decline.Methods: A literature search for randomized trials that included repeated spirometry with at least one active and one placebo arm was conducted. Articles were excluded if study duration was <1 year, <3 spirometric measurements, or <100 subjects per arm. Study design was assessed using the Jadad score. To combine studies and find the estimated effect, we used random effects methodology to account for both within-study and between-study variation.Measurements and Main Results: There were 33,051 patients in the analysis (active component, n = 21,941; placebo, n = 11,110 in nine studies). The active treatment arms demonstrated a 5.0 ml/yr reduction (95% confidence interval, 0.8-9.1 ml/yr; P < 0.001) in the rate of FEV1 decline compared with the placebo arms. The relative FEV1 differences between active and placebo arms were within the range of differences reported for health status and for the exacerbation rate in the same studies.Conclusions: In chronic obstructive pulmonary disease, pharmacotherapy ameliorates rate of lung function decline. The relative benefit observed is within the range of those reported for health status and exacerbations in the same studies. Guidelines should be adjusted according to these findings.