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Innovation is needed for the growing number of patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) is effective in improving exercise tolerance and quality of life, but these benefits do not appear to be sustained. This highlights the need for cost effective methods to maintain benefits on completion of therapy. The findings of a large trial from the UK are reported.
Methods
A two-center randomized controlled trial of patients discharged from PR compared the costs and benefits of PR maintenance with standard care. National Health Service (NHS) resource use, personal expenditure, and societal costs were recorded over one year, and bottom-up costing was undertaken for the PR maintenance program. Changes in health-related quality of life were recorded using the EQ-5D-5L, and differences were compared with the level identified as significant for COPD. A cost utility analysis was undertaken from an NHS perspective; uncertainties in cost and outcome data were incorporated into a sensitivity analysis. Cost-effectiveness ratios and cost-effectiveness acceptability curves (CEACs) were computed.
Results
The study included 116 patients who had finished PR within the last four weeks. The economic analysis showed that mean healthcare costs per patient for PR maintenance were approximately GBP139.72 (EUR165.57) lower than for usual care. The observed 0.118 advantage in mean quality-adjusted life-years (QALYs) (p<0.05) was above the threshold (0.051) for COPD significance. CEACs indicated there was a 97 percent chance of achieving GBP20,000 (EUR23,699.80) per QALY (NICE acceptance level ≤GBP30,000 (EUR35,549.70). Patient and societal costs increased this percentage. It was estimated that if patients with COPD completed a maintenance program following PR, the NHS could save up to GBP28.6 million (EUR33.89 million).
Conclusions
Our findings confirm that a structured PR maintenance program is highly cost effective in extending the benefits of short-term PR. The trial, undertaken during COVID, also signals the potential for emerging digital innovations to provide future transformative change in delivering self-management programs to sustain health and reduce NHS costs for people living with chronic conditions.
The COVID-19 pandemic has catalyzed a move from face-to-face to online delivery of services by hospitals and primary care providers, but little is known about the impact of digital transformation in organizations supporting unpaid caregivers. The value of care provided by informal caregivers since the start of the COVID-19 pandemic has been estimated at EUR111 billion in England.
Methods
The study assessed the impact of digital transformation in an English caregivers’ support organization covering a population of 0.98 million. A retrospective mixed method study was conducted of digital and non-digital support service utilization among caregivers in city and rural geographical areas from January 2019 to June 2021. Organizational performance and service quality indicators were compared for two financial years: 2019-2020 and 2020-2021. A survey of users was conducted to evaluate barriers to and facilitators of digital service uptake, computer proficiency among caregivers, and preferences for future digital service provision.
Results
The number of caregivers registered with the organization rose by 36 percent to 20,237 in 2021. Monthly contacts rose by 225 percent to 6,500, with remote contacts rising from 65 to 85 percent. Observed behavior patterns differed between city and rural caregivers. Overall, one-to-one contacts increased by 89 percent and caregiver assessments by 21 percent, with no expansion in staffing. User-reported service quality improved in five out of eight indicators (p<0.05). The demographic characteristics of survey respondents (152 caregivers) were similar to all registered caregivers. The mean short form Computer Proficiency Questionnaire score of 25.61 indicated a relatively high computer proficiency. Qualitative analysis confirmed a preference for face-to-face and online options. The most highly rated online services were peer support groups and wellbeing assessment and support needs checks.
Conclusions
Considering the economic importance of unpaid caregivers, more attention should be paid to the organizations supporting them and the potential for technology to enhance caregivers’ access to and benefit from such services. This initial assessment of digital transformation in one such organization demonstrates the potential for cost-effective service transition. Further research is required to inform sustainable future solutions.
The incidence of facial palsy has been rising worldwide, with recent evidence emerging of links to COVID-19 infection. To date, guidance on cost-effective treatments is limited to medication (prednisolone). In terms of physical therapy, neuromuscular retraining (NMR) to restore balanced facial function has been most widely evaluated, but not in terms of cost effectiveness. The added value of telerehabilitation is unknown.
Methods
A multistage technology assessment was conducted, which included the following:
• a national survey of current therapy pathways in the UK and patients’ and clinicians’ views on the benefits and challenges of telerehabilitation;
• a systematic review of clinical effectiveness trials evaluating facial NMR therapy;
• calculation of long-term morbidity costs (national economic burden) based on incidence, patient recovery profiles, health-related quality of life, and national facial palsy treatment costs (valuation of clinical improvements in monetary terms was provided by a national Delphi panel); and
• evaluation of the cost effectiveness of telerehabilitation (remote monitoring wearables) added to current face-to-face NMR delivery.
Results
Nationally, approximately five percent of patients with facial palsy (17% of unresolved cases) are referred for facial NMR. The long-term economic burden associated with unresolved cases is estimated to range from GBP351 (EUR417) to GBP584 (EUR692) million, indicating substantial savings if long-term recovery can be improved. Medical treatment costs are GBP86.34 (EUR102) million per annual cohort, and physical and psychological therapy costs are GBP643,292 (EUR762,561). Economic modeling showed that telerehabilitation was cost effective, producing a health gain and a cost-saving of GBP468 (EUR555) per patient. If scaled to the national level for all patients who do not recover fully, an annual saving of GBP3.075 (EUR3.65) million is possible.
Conclusions
Economic modeling indicates that NMR could improve patient outcomes and reduce costs. The national survey demonstrated that access to NMR therapy services is limited, so introduction of telerehabilitation could improve access for currently underserved populations. Future clinical trials need to incorporate economic evaluations to help inform decision-making.
Evidence-based insertion and maintenance bundles are effective in reducing the incidence of central line-associated bloodstream infections (CLABSI) in intensive care unit (ICU) settings. We studied the adoption and compliance of CLABSI prevention bundle programs and CLABSI rates in ICUs in a large network of acute care hospitals across Canada.
The proliferation, metastasis and therapy response of tumour cells are tightly regulated by interaction among various signalling networks. The microRNAs (miRNAs) can bind to 3′-UTR of mRNA and down-regulate expression of target gene. The miRNAs target various molecular pathways in regulating biological events such as apoptosis, differentiation, angiogenesis and migration. The aberrant expression of miRNAs occurs in cancers and they have both tumour-suppressor and tumour-promoting functions. On the contrary, SOX proteins are capable of binding to DNA and regulating gene expression. SOX2 is a well-known member of SOX family that its overexpression in different cancers to ensure progression and stemness. The present review focuses on modulatory impact of miRNAs on SOX2 in affecting growth, migration and therapy response of cancers. The lncRNAs and circRNAs can function as upstream mediators of miRNA/SOX2 axis in cancers. In addition, NF-κB, TNF-α and SOX17 are among other molecular pathways regulating miRNA/SOX2 axis in cancer. Noteworthy, anti-cancer compounds including bufalin and ovatodiolide are suggested to regulate miRNA/SOX2 axis in cancers. The translation of current findings to clinical course can pave the way to effective treatment of cancer patients and improve their prognosis.
In this narrative review we consider what is known about mental health conditions in the prison system in Bangladesh and describe the current provision of mental health services for prisoners with mental health needs. We contextualise this within the literature on mental health conditions in correctional settings in the wider sub-continental region and low- and middle-income countries (LMICs) more broadly. We augment findings from the literature with information from unstructured interviews with local experts, and offer recommendations for research, policy and practice.
High temperature negatively affects cotton production worldwide. In Pakistan, cotton crop faces high temperature at peak flowering during June–July, which is a major reason for yield losses. The present study was conducted to find some agro-physiological markers for high-temperature tolerance. Fifty cotton genotypes were raised under normal sown (high-temperature stress) and late sown (optimum temperature) conditions for 2 years. Data were recorded for relative cell injury percentage (RCI), chlorophyll content (CC), canopy temperature (CT), boll retention percentage (BR), bolls per plant (BP), boll weight (BW), hundred seed weight (HSW), sympodial branches per plant (SBP), plant height (PH) and seed cotton yield (SCY). A large amount of variability was found among cotton genotypes as proved by descriptive statistics. Stable genotypes were selected based on higher SCY and yield components (BP, BW, HSW, SBP, PH and SCY) performance along with less RCI%, high CC and low CT. The results of heatmap analysis showed that the six cotton genotypes viz., FH-Noor, FH-Lalazar, FH-458, FH-466, NIAB-545 and NIAB-878 performed better under high-temperature stress. These selected genotypes can be a source for breeding high-temperature tolerance. Furthermore, the results from correlation analysis confirmed that the traits such as RCI%, CC and CT can be considered as early selection criteria due to their positive association with SCY. Whilst some other parameters such as BP, BW, BR, SBP and PH might be used as direct selection indices for SCY under high-temperature stress.
In the United Kingdom (UK), 23,000 people annually are diagnosed with facial palsy (acute onset facial paralysis). For nearly one third this will result in a permanent disability, including in some the inability to smile. In addition to initial pharmacological therapy, guidelines recommend tailored facial exercise (TFE) therapy repeated every day. However, not all patients are currently able to access such specialist physical therapy. ‘Smart specs’ (using miniaturized sensors in the frames to measure facial movement) are currently being developed. Linked to a smartphone, these could allow people to practice TFEs discreetly, provide immediate feedback, and supply data on outcomes to the patient and their clinician.
Methods:
Modelling of introduction of Facial Remote Activity Monitoring Eyewear (FRAME) into treatment pathways for patients with facial palsy. This included: (i) review on effectiveness of TFE therapy; (ii) national surveys (medical staff, facial therapy specialists and patients) to gather data on access to TFE therapy; (iii) Delphi Exercise to identify consensus on key outcome measures; and, (iv) economic modelling to estimate cost-effectiveness and determine a range of acceptable costs for the technology. In parallel, research to examine target markets to inform product development, and production of integral commercialization plan.
Results:
Searches short-listed ten studies to add to the three included in the 2011 Cochrane review. Surveys indicate approximately thirteen percent of eligible UK patients access personalized TFE therapy. Estimated annual expenditure on hospital treatments for facial palsy patients is currently >GBP 80 million (>USD 106 million) compared with <GBP 0.5 million (<USD 0.66 million) on TFE therapy. Patients with permanent defects can suffer a loss of up to two quality-adjusted life years (QALYs).
Conclusions:
Findings from this study, particularly in relation to costs and benefits, will inform the design of a subsequent randomized controlled trial. A novel wearable technology could make a major difference to people's lives, as well as generating potential efficiencies for healthcare.
In this paper, we present the electromagnetic modeling of a performance-enhanced planar Schottky diode for applications in terahertz (THz) frequencies. We provide a systematic simulation approach for analyzing our Schottky diode based on finite element method and lumped equivalent circuit parameter extraction. Afterward, we use the developed model to investigate the effect of design parameters of the Schottky diode on parasitic capacitive and resistive elements. Based on this model, device design has been improved by deep-trench formation in the substrate and using a closed-loop junction to reduce the amount of parasitic capacitance and spreading resistance, respectively. The results indicate that cut-off frequency can be improved from 4.1 to 14.1 THz. Finally, a scaled version of the diode is designed, fabricated, and well characterized to verify the validity of this modeling approach.
A.C. Bradley's use of character criticism as a means of explaining tragedy away is not a pitfall he is insensitive to. Bradley recognises that the very act of explaining risks explaining (something like tragedy) away.
Any answer we give to the question [of the source of tragic power] … ought to correspond with, or to represent in terms of the understanding, our imaginative and emotional experience in reading the tragedies. We have, of course, to do our best by study and effort to make this experience true to Shakespeare; but, that done to the best of our ability, the experience is the matter to be interpreted, and the test by which the interpretation must be tried. But it is extremely hard to make out exactly what this experience is, because, in the very effort to make it out, our reflecting mind, full of everyday ideas, is always tending to transform it by the application of these ideas, and so to elicit a result which, instead of representing the fact, conventionalizes it. And the consequence is not only mistaken theories; it is that many a man will declare that he feels in reading a tragedy what he never really felt, while he fails to recognize what he actually did feel. It is not likely that we shall escape all these dangers in our effort to find an answer to the question regarding the tragic world and the ultimate power in it.
Why should conventionalising Shakespeare's tragedies be more of a threat today than when Bradley wrote in 1904, enough of a threat to warrant radically different interpretive approaches? One reason is that the historicist method entails the types of misperceptions that Bradley alludes to: a replacement of feeling with explanation and, in time, convention. However unlikely it may be that interpretation can avoid conventionalising the tragic effect, Bradley is sympathetic to critical efforts attempting as much. Yet he, or at least the manner in which his brand of character criticism has been taken up, also consigns us to searching for conventional prescriptive answers, if not in the immediate historical contingencies of Elizabethan England, then in definitive character traits, known in tragedy as ‘flaws’.
To consider counterfactual possibilities is to consider, and to want to rescue, a character's freedom. It reflects a critical desire to break from limitations, or limitations of convention. In Macbeth, we are presented with a prophecy that seems to limit the possible ways the play could end. In Hamlet we are given not prophecy, but testimony, which does not restrict Hamlet's freedom in the same way. It makes sense for both Hamlet and us as readers to question the veracity of the Ghost's story. We can conceive of the possibility of the Ghost as a ‘Goblin damned’ (1.4.21), however much we may want its testimony to be true. In Macbeth, on the other hand, to ask something like ‘What if the prophecies aren't true?’ would be to ask, ‘If not, why would Shakespeare give them to us?’ And there is no answer other than to reiterate that because he does, it is by matter of conventional necessity that they come true. Hence no serious critical effort can question the veracity of the sisters’ prophecy in the way Greg called ‘Hamlet's hallucination’ into question. The Ghost's appearance in Hamlet does not dictate as explicitly in what manner Hamlet ought to unfold. The sisters’ prophecy, on the other hand, does have immediate bearing on how Macbeth, and not Macbeth, should end. At some point, Macbeth must serve, or have served, as king. This suggests that Macbeth is far more beholden to outer necessity rather than inner contingency, which further shrinks his sphere of individuality and hence his freedom. So how indeed to (re)capture Macbethe's freedom? If it is imperative for us, as readers, to remember that Macbeth is free, we must consider what sort of critical price we are willing to pay for his freedom.
One way would be to delay, as long as possible, a definitive reading of the precise arrival of Macbeth's ambition. Where Hamlet is burdened by the (im)possibility of correct action, Macbeth is burdened by the (im)possibility of correct thought. Hamlet desires thought as an end to all thinking, as though once armed with correct thought, correct action can only follow. Macbeth operates at an opposite metaphysical pole. He desires correct action as an end to all action, as though once the correct action is carried out, he will no longer be burdened by his desires.
I am making the case that Shakespeare criticism is caught in a dialectical trap. In the aggregate, Shakespeare verifies either our freedom or our unfreedom. In the current critical climate, counterfactual thinking could only be read as a type of character criticism, or renewal of Bradleyan character criticism. However, Bradley's ‘flaws’ are not discovered; they are applied to the text in advance, quashing character freedom. Counterfactual criticism attempts to recover this freedom by emphasising the play of outer contingency over inner necessity. Yet moving forward, no critical law dictates that considering counterfactuals demands the discussion of character over events, as character is no doubt shaped by events anyway. In the matrix of contingencies available in the present, it may now be worth emphasising character choice. But the discussion of possible events could just as easily lead the conversation of counterfactual thinking. Where character meets event is a contested site, not in presupposing other factors to clash there, but in acknowledging that each exists in juxtaposition to the other. Neither side can be verified as true once and for all. Put simply, a charactere's freedom is not a stable entity or personality trait that said character simply accepts or denies, as though it is our critical lot to establish whether or not he does that. Rather, it is to reiterate that just because a character chooses does not constitute a fate, which is a negation of choice. A character, of course, must choose. Macbeth makes his choice, which is, in his peculiar case, an attempt to negate choice and action, which could have been achieved more readily (but less dramatically) had he chosen to do nothing. But after Macbeth chooses, critics who comment on Macbeth or anyone else after the fact will be tempted to seek out a dangerous sort of knowledge – one that must come up with ways, whether aesthetic, psychological or material, to explain why said character chose one way and not another, wanting to believe that by choosing alone, said character has relinquished his freedom. But freedom exists only when possibilities are open. Just because one choice is made over another does not mean that one had to choose that one, out of necessity, over the others. Yet this is the rabbit any propositional criticism will chase out eternally.
Negative capability, that is when man is capable of being in uncertainties, mysteries, doubts, without any irritable reaching after fact and reason – Coleridge, for instance, would let go by a fine isolated verisimilitude caught from the Penetralium of mystery, from being incapable of remaining content with half knowledge.
John Keats
Now to me the total works of Shakespeare are like a very, very complete set of codes and these codes, cipher for cipher, set off in us, stir in us, vibrations and impulses which we immediately try to make coherent and understandable.
Peter Brook
Discussing tragedy is tricky business. One is immediately tempted to outline a definition of tragedy, or, at the very least, to account for certain criteria that allow it to function. What this project proposes instead are reading strategies that will allow a ‘tragic effect’ to resonate. In particular, this project makes a case for reading ‘in the present’, what Stanley Cavell calls inhabiting ‘an experience of continuous presentness’. The most expedient way to do this will be to consider alternative possibilities to the accepted linear (narrative) developments of the plays at hand: assuming Macbeth had done x instead of y, for example, or that we, as readers, know x and not y. Yet this not in order to get away from the narrative unfolding of a play but, on the contrary, to become more intimate with it. These readings will be defined, somewhat loosely, as ‘counterfactual’ readings. Furthermore, the tragic effect will be linked to ‘discovery’– what Northrop Frye, and before him Aristotle, calls ‘anagnorisis’ – emphasising in particular a sense of ‘wonder’. This project argues that (1) the sorts of discoveries to be made are those that reveal or sustain a sense of wonder, the ‘uncertainties, mysteries, doubts’ that Keats associates with ‘negative capability’, and (2) this sense of wonder is key to the functioning of tragedy. Therefore, what is to be discovered cannot be prescribed because if we articulate beforehand just what it is we are looking for, we have removed ourselves from the realm of negative capability and, just because of that, the tragic effect is lost. One could make the case that these plays, in order to be tragic, must initiate a discovery procedure.