62 research outputs found
Development of a Physical Therapy Faculty Workload Measurement Tool
Counting credit hours is not an equitable way to measure faculty workload in physical therapy education considering online delivery with heavy workloads negatively impacting satisfaction, learning outcomes, and research productivity. The University of St. Augustine for Health Sciences (USAHS) is a graduate-level institution in the United States, with seven Doctor of Physical Therapy programs offered in four US locations. USAHS faculty workload includes 50% teaching, 20% scholarship, 30% a combination of service, administration, release, and discretionary time. The aim of this study was to develop a faculty workload measurement tool that quantifies productivity, was easy to use, and equitable. Two large faculty pilots were completed; data and open-ended responses were used to develop a final version of the workload measurement tool to be fully implemented in late 2018. The task force developed a workload measurement tool that appears to be accurate, transparent, and impartial. With the addition of directions and the self-calculating formulas, the form provides quick, consistent information to faculty and their supervisors regarding the division of workload between the four main areas of faculty time
Consolidated standards of reporting trials (CONSORT) and the completeness of reporting of randomised controlled trials (RCTs) published inmedical journals (Review)
Background: An overwhelming body of evidence stating that the completeness of reporting of randomised controlled trials (RCTs) is not optimal
has accrued over time. In the mid-1990s, in response to these concerns, an international group of clinical trialists, statisticians,
epidemiologists, and biomedical journal editors developed the CONsolidated Standards Of Reporting Trials (CONSORT) Statement.
The CONSORT Statement, most recently updated in March 2010, is an evidence-based minimum set of recommendations including
a checklist and flow diagram for reporting RCTs and is intended to facilitate the complete and transparent reporting of trials and aid
their critical appraisal and interpretation. In 2006, a systematic review of eight studies evaluating the āeffectiveness of CONSORT in
improving reporting quality in journalsā was published.
Objectives: To update the earlier systematic review assessing whether journal endorsement of the 1996 and 2001 CONSORT checklists influences
the completeness of reporting of RCTs published in medical journals.
Search methods: We conducted electronic searches, known item searching, and reference list scans to identify reports of evaluations assessing the
completeness of reporting of RCTs. The electronic search strategy was developed inMEDLINE and tailored to EMBASE.We searched
the Cochrane Methodology Register and the Cochrane Database of Systematic Reviews using the Wiley interface. We searched the
Science Citation Index, Social Science Citation Index, and Arts and Humanities Citation Index through the ISI Web of Knowledge
interface. We conducted all searches to identify reports published between January 2005 and March 2010, inclusive.
Selection criteria: In addition to studies identified in the original systematic review on this topic, comparative studies evaluating the completeness of
reporting of RCTs in any of the following comparison groups were eligible for inclusion in this review: 1) Completeness of reporting
of RCTs published in journals that have and have not endorsed the CONSORT Statement; 2) Completeness of reporting of RCTs
published in CONSORT-endorsing journals before and after endorsement; or 3) Completeness of reporting of RCTs before and after
the publication of the CONSORT Statement (1996 or 2001). We used a broad definition of CONSORT endorsement that includes
any of the following: (a) requirement or recommendation in journalās āInstructions to Authorsā to follow CONSORT guidelines; (b)
journal editorial statement endorsing the CONSORT Statement; or (c) editorial requirement for authors to submit a CONSORT
checklist and/or flow diagram with their manuscript. We contacted authors of evaluations reporting data that could be included in
any comparison group(s), but not presented as such in the published report and asked them to provide additional data in order to
determine eligibility of their evaluation. Evaluations were not excluded due to language of publication or validity assessment.
Data collection and analysis: We completed screening and data extraction using standardised electronic forms, where conflicts, reasons for exclusion, and level
of agreement were all automatically and centrally managed in web-based management software, DistillerSRĀ®. One of two authors
extracted general characteristics of included evaluations and all data were verified by a second author. Data describing completeness of
reporting were extracted by one author using a pre-specified form; a 10%random sample of evaluations was verified by a second author.
Any discrepancies were discussed by both authors; we made no modifications to the extracted data. Validity assessments of included
evaluations were conducted by one author and independently verified by one of three authors. We resolved all conflicts by consensus.
For each comparison we collected data on 27 outcomes: 22 items of the CONSORT 2001 checklist, plus four items relating to the
reporting of blinding, and one item of aggregate CONSORT scores. Where reported, we extracted and qualitatively synthesised data
on the methodological quality of RCTs, by scale or score.
Main results: Fifty-three publications reporting 50 evaluations were included. The total number of RCTs assessed within evaluations was 16,604
(median per evaluation 123 (interquartile range (IQR) 77 to 226) published in a median of six (IQR 3 to 26) journals. Characteristics of
the included RCT populations were variable, resulting in heterogeneity between included evaluations. Validity assessments of included
studies resulted in largely unclear judgements. The included evaluations are not RCTs and less than 8% (4/53) of the evaluations
reported adjusting for potential confounding factors.
Twenty-five of 27 outcomes assessing completeness of reporting in RCTs appeared to favour CONSORT-endorsing journals over
non-endorsers, of which five were statistically significant. āAllocation concealmentā resulted in the largest effect, with risk ratio (RR)
1.81 (99% confidence interval (CI) 1.25 to 2.61), suggesting that 81% more RCTs published in CONSORT-endorsing journals
adequately describe allocation concealment compared to those published in non-endorsing journals. Allocation concealment was
reported adequately in 45% (393/876) of RCTs in CONSORT-endorsing journals and in 22% (329/1520) of RCTs in non-endorsing
journals. Other outcomes with results that were significant include: scientific rationale and background in the āIntroductionā (RR 1.07,
99% CI 1.01 to 1.14); āsample sizeā (RR 1.61, 99% CI 1.13 to 2.29); method used for āsequence generationā (RR 1.59, 99% CI 1.38
to 1.84); and an aggregate score over reported CONSORT items, ātotal sum scoreā (standardised mean difference (SMD) 0.68 (99%
CI 0.38 to 0.98)).
Authorsā conclusions: Evidence has accumulated to suggest that the reporting of RCTs remains sub-optimal. This review updates a previous systematic review
of eight evaluations. The findings of this review are similar to those from the original review and demonstrate that, despite the general
inadequacies of reporting of RCTs, journal endorsement of the CONSORT Statement may beneficially influence the completeness
of reporting of trials published in medical journals. Future prospective studies are needed to explore the influenc
Antidepressant treatment with sertraline for adults with depressive symptoms in primary care : the PANDA research programme including RCT
Background Despite a growing number of prescriptions for antidepressants (over 70 million in 2018), there is uncertainty about when people with depression might benefit from antidepressant medication and concern that antidepressants are prescribed unnecessarily. Objectives The main objective of the PANDA (What are the indications for Prescribing ANtiDepressAnts that will lead to a clinical benefit?) research programme was to provide more guidance about when antidepressants are likely to benefit people with depression. We aimed to estimate the minimal clinically important difference for commonly used self-administered scales for depression and anxiety, and to understand more about how patients respond to such assessments. We carried out an observational study of patients with depressive symptoms and a placebo-controlled randomised controlled trial of sertraline versus placebo to estimate the treatment effect in UK primary care. The hypothesis was that the severity and duration of symptoms were related to treatment response. Design The programme consisted of three phases. The first phase relied on the secondary analysis of existing data extracted from published trials. The second phase was the PANDA cohort study of patients with depressive symptoms who presented to primary care and were followed up 2, 4 and 6 weeks after a baseline assessment. Both quantitative and qualitative methods were used in the analysis. The third phase was a multicentre randomised placebo-controlled double-blind trial of sertraline versus placebo in patients presenting to primary care with depressive symptoms. Setting UK primary care in Bristol, London, Liverpool and York. Participants Patients aged 18ā74 years who were experiencing depressive symptoms in primary care. Eligibility for the PANDA randomised controlled trial included that there was uncertainty about the benefits about treatment with an antidepressant. Interventions In the PANDA randomised controlled trial, patients were individually randomised to 100āmg daily of sertraline or an identical placebo. The PANDA cohort study was an observational study. Main outcome measures Depressive symptoms measured using the Patient Health Questionnaire were the primary outcome for the randomised controlled trial. Other outcomes included anxiety symptoms using the Generalised Anxiety Disorder-7; depressive symptoms using the Beck Depression Inventory, version 2; health-related quality of life; self-reported improvement; and cost-effectiveness. Results The secondary analysis of existing randomised controlled trials [GENetic and clinical Predictors Of treatment response in Depression (GenPod), TREAting Depression with physical activity (TREAD) and Clinical effectiveness and cost-effectiveness of cognitive Behavioural Therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care (CoBalT)] found evidence that the minimal clinically important difference increased as the initial severity of depressive symptoms rose. Our estimates of minimal clinically important difference were a 17% and 18% reduction in Beck Depression Inventory scores for GenPod and TREAD, respectively. In CoBalT, a 32% reduction corresponded to the minimal clinically important difference but the participants in this study had depression that had not responded to antidepressants. In the PANDA study cohort, and from our analyses in existing data, we found that the minimal clinically important difference varies considerably with the initial severity of depressive and anxiety symptoms. Expressing the minimal clinically important difference as a percentage reduction reduces this variation at higher scores, but at low scores the percentage reduction increased substantially. The results from the qualitative studies pointed out many limitations of the Patient Health Questionnaire-9 items in assessing change and recovery from depression. In the PANDA randomised controlled trial, there was no evidence that sertraline resulted in a reduction in depressive symptoms within 6 weeks of randomisation, but there was some evidence of a reduction by 12 weeks. However, sertraline led to a reduction in anxiety symptoms, an improvement of mental health-related quality of life and an increased likelihood of reporting improvement. The mean Patient Health Questionnaire-9 items score at 6 weeks was 7.98 (standard deviation 5.63) in the sertraline group and 8.76 (standard deviation 5.86) in the placebo group (5% relative reduction, 95% confidence interval ā7% to 15%; pā=ā0.41). Of the secondary outcomes, there was strong evidence that sertraline reduced anxiety symptoms (Generalised Anxiety Disorder-7 score reduced by 17% (95% confidence interval 9% to 25%; pā=ā0.00005). Sertraline had a high probability (>ā90%) of being cost-effective at 12 weeks. The PANDA randomised controlled trial found no evidence that treatment response or cost-effectiveness was related to severity or duration of depressive symptoms. The minimal clinically important difference estimates suggested that sertralineās effect on anxiety, but not on depression, was likely to be clinically important. Limitations The results from the randomised controlled trial and the estimates of minimal clinically important difference were not sufficiently precise to provide specific clinical guidance for individuals. We had low power in testing whether or not initial severity and duration of depressive symptoms are related to treatment response. Conclusions The results of the trial support the use of sertraline and probably other selective serotonin reuptake inhibitors because of their action in reducing anxiety symptoms and the likelihood of longer-term benefit on depressive symptoms. Sertraline could be prescribed for anxiety symptoms that commonly occur with depression and many patients will experience a clinical benefit. The Patient Health Questionnaire-9 items and similar self-administered scales should not be used on their own to assess clinical outcome, but should be supplemented with further clinical assessment. Future work We need to examine the longer-term effects of antidepressant treatment. We need more precise estimates of the treatment effects and minimal clinically important difference at different severities to provide more specific guidance for individuals. However, the methods we have developed provide an approach towards providing such detailed guidance. Trial registration Current Controlled Trials ISRCTN84544741 and EudraCT number 2013-003440-22. Funding This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 10. See the NIHR Journals Library website for further project information
Mutant profilin1 transgenic mice recapitulate cardinal features of motor neuron disease
The recent identiļ¬cation of proļ¬lin1 mutations in 25 familial ALS cases has linked altered function of this cytoskeletonregulating protein to the pathogenesis of motor neuron disease. To investigate the pathological role of mutant proļ¬lin1 in motor neuron disease, we generated transgenic lines of mice expressing human proļ¬lin1 with a mutation at position 118 (hPFN1G118V). One of the mouse lines expressing high levels of mutant human PFN1 protein in the brain and spinal cord exhibited many key clinical and pathological features consistent with human ALS disease. These include loss of lower (ventral horn) and upper motor neurons (corticospinal motor neurons in layer V), mutant proļ¬lin1 aggregation, abnormally ubiquitinated proteins, reduced choline acetyltransferase (ChAT) enzyme expression, fragmented mitochondria, glial cell activation, muscle atrophy, weight loss, and reduced survival. Our investigations of actin dynamics and axonal integrity suggest that mutant PFN1 protein is associated with an abnormally low ļ¬lamentous/globular (F/G)-actin ratio that may be the underlying cause of severe damage to ventral root axons resulting in a Wallerian-like degeneration. These observations indicate that our novel proļ¬lin1 mutant mouse line may provide a new ALS model with the opportunity to gain unique perspectives into mechanisms of neurodegeneration that contribute to ALS pathogenesis
Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
The Effect of Bevacizumab on Human Malignant Melanoma Cells with Functional VEGF/VEGFR2 Autocrine and Intracrine Signaling Loops
Receptors for the angiogenic factor VEGF are expressed by tumor cancer cells including melanoma, although their functionality remains unclear. Paired human melanoma cell lines WM115 and WM239 were used to investigate differences in expression and functionality of VEGF and VEGFR2 in vitro and in vivo with the anti-VEGF antibody bevacizumab. Both WM115 and WM239 cells expressed VEGF and VEGFR2, the levels of which were modulated by hypoxia. Detection of native and phosphorylated VEGFR2 in subcellular fractions under serum-free conditions showed the presence of a functional autocrine as well as intracrine VEGF/VEGFR2 signaling loops. Interestingly, treatment of WM115 and WM239 cells with increasing doses of bevacizumab (0ā300 Āµg/ml) in vitro did not show any significant inhibition of VEGFR2 phosphorylation. Small-molecule tyrosine kinase inhibitor, sunitinib, caused an inhibition of VEGFR2 phosphorylation in WM239 but not in WM115 cells. An increase in cell proliferation was observed in WM115 cells treated with bevacizumab, whereas sunitinib inhibited proliferation. When xenografted to immune-deficient mice, we found bevacizumab to be an effective antiangiogenic but not antitumorigenic agent for both cell lines. Because bevacizumab is unable to neutralize murine VEGF, this supports a paracrine angiogenic response. We propose that the failure of bevacizumab to generate an antitumorigenic effect may be related to its generation of enhanced autocrine/intracrine signaling in the cancer cells themselves. Collectively, these results suggest that, for cancers with intracrine VEGF/ VEGFR2 signaling loops, small-molecule inhibitors of VEGFR2 may be more effective than neutralizing antibodies at disease control
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