The role of accelerator programmes in supporting the adoption of digital health technologies: A qualitative study of the perspectives of small- and medium-sized enterprises.

Objective: Evidence-based digital health technologies are increasingly important in delivering care to an ageing population with constrained resources. In the United Kingdom, accelerator programmes (APs) have been developed to support the adoption of digital health technologies within the National Health Service. This study aims to explore the perspectives of stakeholders using APs. Methods: Stakeholders representing nine small -and medium-sized enterprises (SMEs) that were engaged with three different APs (n = 9). Semi-structured interviews were conducted with key informants between April and September 2018. Framework analysis of the data was performed to explore their perspectives on APs. Results: Four key themes were generated. Informants reported the need to generate evidence before and during the programme, appreciating different types of evidence and their importance. Informants identified several key factors that were a catalyst for success, including involvement in the programme and access to individuals and organisations that were crucial for support. However, several barriers were identified at the programme and system levels. Finally, informants identified key supporting processes that enhanced the adoption of their innovations. Conclusion: SMEs that develop digital health technologies report that, while APs are useful in supporting the adoption of these technologies, some issues remain. These relate to the emphasis on traditional research evidence that remains a challenge for SMEs to generate. Also, several system-level barriers to innovation in healthcare persist. As APs and SMEs continue to create an entrepreneurial ecosystem, there is increased potential for the development of supporting processes and infrastructure to accelerate the efficient and timely adoption of new digital health technologies.

The coronavirus disease clavicle study: a predictor of future trauma trends.

Background: Clavicle fractures are a common presentation to the emergency department after falls and sporting injuries. During 2020, the coronavirus disease 2019 (COVID-19) pandemic brought with it a long period of social isolation, resulting in a change of behavior patterns and, in return, the presentation of fractures to our local hospitals. The effects of this global pandemic on the presentation and management of clavicles were noted with particular interest to the change in mechanism and its future implications. Methods: We performed a longitudinal observational study in 10 hospitals in the North West of England, reviewing all patients presenting with a clavicle fracture during 6 weeks in the first peak of COVID-19 pandemic and compared these with the same period in 2019. Collection points included the patient demographics, fracture characteristics, mechanism of injury, and management. Results: A total of 427 clavicle fractures were assessed with lower numbers of patients presenting with a clavicle fracture during the COVID-2020 period (n = 177) compared with 2019 (n = 250). Cycling-related clavicle fractures increased 3-fold during the pandemic compared with the 2019 control group. We also noted an overall increase in clavicle fractures resulting from higher energy trauma as opposed to low energy or fragility fracture. We also found a faster time to surgery in the COVID cohort by 2.7 days on average when compared with 2019. Conclusions: Government restrictions and the encouragement of social distancing led to behavioral changes with a vast increase in cyclists on the road. This created a significant rise in clavicle fractures related to this activity. This is likely to be further driven by the government pledge to double cyclists on the road by 2025 in the United Kingdom. We forecast that this increase in cyclists, a behavior change accelerated by the pandemic, is a reliable predictor for future trauma trends.

Preconsultation Questionnaires for Patients Attending Elective Foot and Ankle Clinics: Is This the Way Forward in Outpatient Clinics?

Orthopaedic clinics can often be overbooked' busy and delayed appointments are a common sight in the National Health Service. We recognize this is becoming a growing problem that needs to be addressed; therefore, we have carried out a quality improvement project (QIP) that can save clinicians time. We have developed the "Stockport Foot and Ankle Questionnaire," a novel preconsultation questionnaire to gather information about patient history and symptoms. We found that the average time required for consultation reduced from a mean of 22 minutes, without questionnaires, to a mean of 15 minutes with the questionnaire, effectively saving 7 minutes per consultation. The preconsultation questionnaire in foot and ankle clinics is a novel technique to improve efficiency, productivity, and standardization in outpatient clinics. It is a patient-centered approach that identifies where effective changes can be implemented in how outpatient services are run. We recommend routine use of these questionnaires to save valuable clinician time.Levels of Evidence: Level II.

Heavy Metal Contamination in Soils and Crops Irrigated by Kali River in Uttar Pradesh, India.

The study investigated concentrations, distribution, and bioaccumulation of heavy metals in agriculture soil and crops irrigated by the Kali River of Uttar Pradesh, India. Soils and crop samples were collected from 17 locations along the river and analyzed for heavy metal concentrations. Metals in soil and plant were recorded as Fe > Zn > Mn > Cu > Ni > Pb > Cr > Cd and Mn > Fe > Zn > Cu > Cr > Ni > Pb > Cd, respectively. The bioaccumulation factor was < 1 that indicates lesser accumulation of metals in plants except for Cd, Mn, and Zn. Metal pollution index ranged between 1.84 and 6.62 and shows that crops growing at the S10 to S17 sites accumulate greater metal concentrations. Cluster analysis showed agglomeration of Cr-Pb-Cd, Cu-Ni-Mn, and Fe-Zn which revealed different sources of metal pollution. The present study shows low to moderate heavy metal pollution in Kali River irrigated areas thus consumption of agriculture produce may cause adverse health effects.

The NICE Evidence Standards Framework for digital health and care technologies - Developing and maintaining an innovative evidence framework with global impact.

OBJECTIVE: In 2018, the UK National Institute for Health and Care Excellence (NICE), in partnership with Public Health England, NHS England, NHS Improvement and others, developed an evidence standards framework (ESF) for digital health and care technologies (DHTs). The ESF was designed to provide a standardised approach to guide developers and commissioners on the levels of evidence needed for the clinical and economic evaluation of DHTs by health and care systems. METHODS: The framework was developed using an agile and iterative methodology that included a literature review of existing initiatives and comparison of these against the requirements set by NHS England; iterative consultation with stakeholders through an expert working group and workshops; and questionnaire-based stakeholder input on a publicly available draft document. RESULTS: The evidence standards framework has been well-received and to date the ESF has been viewed online over 55,000 times and downloaded over 19,000 times. CONCLUSIONS: In April 2021 we published an update to the ESF. Here, we summarise the process through which the ESF was developed, reflect on its global impact to date, and describe NICE's ongoing work to maintain and improve the framework in the context for a fast moving, innovative field.

COVID-19 infection is related to differences in the use of personal protective equipment by orthopaedic specialist trainees caring for hip fracture patients during the second surge of COVID-19 in the North West of England.

INTRODUCTION: Personal protective equipment (PPE) may protect health-care workers from COVID-19 infection and limit nosocomial spread to vulnerable hip fracture patients. METHODS: We performed a cross-sectional survey amongst orthopaedic trainees to explore PPE practice in 19 hospitals caring for hip fracture patients in the North West of England. RESULTS: During the second wave of the pandemic, 14/19 (74%) hospitals experienced an outbreak of COVID-19 amongst staff or patients on the orthopaedic wards. An FFP3 respirator mask was used by doctors in only 6/19 (32%) hospitals when seeing patients with COVID-19 and a cough and in 5/19 (26%) hospitals when seeing asymptomatic patients with COVID-19. A COVID-19 outbreak was reported in 11/13 (85%) orthopaedic units where staff wore fluid resistant surgical masks compared to 3/6 (50%) units using an FFP3 respirator mask (RR 1.69, 95% CI 0.74-3.89) when caring for symptomatic patients with COVID-19. Similarly, a COVID-19 outbreak was reported in more orthopaedic units caring for asymptomatic patients with COVID-19 where staff wore fluid resistant surgical masks (12/14 (86%)) as compared to an FFP3 respirator mask (2/5 (40%)) (RR 2.14, 95% CI 0.72-6.4). CONCLUSION: Urgent re-evaluation of PPE use is required to reduce nosocomial spread of COVID-19, amongst highly vulnerable patients with hip fracture.

Assessment of spatial and temporal variations in water quality by the application of multivariate statistical methods in the Kali River, Uttar Pradesh, India.

The Kali River is a significant source of surface water as well as the main tributary of River Hindon that flows through major cities of western Uttar Pradesh, India. It flows throughout the urban and industrial regions; hence, it carries various amounts of pollutant. Therefore, a study was conducted to examine spatial-temporal variations in river water quality by determining physicochemical variables and heavy metal concentrations at seventeen sampling stations (S1-S17) throughout the river stretch. Various physicochemical variables, namely pH, EC, TDS, turbidity, BOD, COD, TH, TA, Ca, Mg, Na, K, HCO3-, Cl-, SO42-, NO3-, and PO43- were higher in summer than in winter. The order of mean metal concentrations was Fe > Pb > Mn > Ni > Zn > Cu > Cr > Cd. The relationships among measured physicochemical variables and pollution index were examined. Furthermore, multivariate statistical methods were used to assess spatial-temporal variation in water quality to identify current pollution sources and validate results. Water quality index and comprehensive pollution index indicated that the Kali River was less polluted from S1 to S8. However, downstream sampling sites were polluted. Pollution starts from S9 and drastically increases at and beyond S13 because of effluents from industries and sugar mills in Muzaffarnagar. The study suggests cleaning the downstream region of river to restore human health and flora and fauna in the river ecosystem.

Impact of municipal wastewater reuse through micro-irrigation system on the incidence of coliforms in selected vegetable crops.

The incidence of coliforms in soil and agricultural produce was evaluated in two vegetable crops, namely, cauliflower and eggplant, which were grown using wastewater for irrigation. Field experiment was conducted at Indian Agricultural Research Institute (IARI), New Delhi, India. In the field experiments to irrigate the crop, municipal wastewater was applied through drip system. The filtration of irrigation water was done through sand media, disk media and their combination. The laterals were placed at surface and subsurface of soil. All filtration processes significantly reduced total coliforms (12-20%) and E. coli (15-25%) populations when evaluated against untreated wastewater. The population dynamics of coliforms in soil profiles indicated that the maximum population of E. coli was estimated on the surface of soil profile when using surface drip, which decreased with soil depth under subsurface placement of drip lateral. After crop harvesting, E. coli in the soil reduced until 20 days after the cessation of irrigation and was highly correlated with soil moisture. E. coli and total coliforms availability were noticed on the surface and in the tissues of leaf and fruit, the coliform count is higher on the surface of plants under surface placement of drip lateral. The concentration of coliforms was lower with eggplant in comparison to cauliflower due to the smooth fruit surface of eggplant. Our study reveals the critical role of subsurface drip irrigation in reducing the load of coliform both in the soil and the crop produce ensuring safety of the consumers against health hazards. In another way protect the environment from wastewater disposal and reduce the burden on synthetic fertilizers as well as shrinking freshwater resources.

Hydrochemical evaluation and identification of geochemical processes in the shallow and deep wells in the Ramganga Sub-Basin, India.

Groundwater samples were collected from 44 wells in the Ramganga Sub-Basin (RSB), India, and analysed for major ions, nutrients and trace metals. The primary goal of this study is to evaluate the hydrochemistry and to identify the geochemical processes that govern the water chemistry in the shallow and deep tube wells in the study area using geochemical methods. The knowledge of changes in hydrochemistry of the aquifers is important for both groundwater recharge and use in the region. This study found that there are substantial differences of water chemistry between shallow and deep wells. In the shallow wells, the average concentrations of total dissolved solid (TDS), Na, K, Ca, Mg, HCO3, Cl, SO4, NO3, PO4, F, Cu, Mn, Fe and Cr are twofold higher than the deep wells. The concentrations of dissolved silica in the groundwater do not vary with the depth, which implies that the variation in the water chemistry is not due to mineral dissolution alone. Major ion ratios and saturation indices suggest that the water chemistry is predominantly controlled by dissolution of carbonate minerals, silicate weathering and ion exchange reactions. Thermodynamic evaluation (ion activity ratios and stability filed diagrams) indicates that the kaolinite and gibbsite controlled the water chemistry in the both shallow and deep wells. In addition, the groundwater chemistry in the shallow wells is affected by the vertical infiltration of contaminated water from surface contamination sources and nitrification process. In the deep wells, absence of NO3 and low concentrations of Cl, SO4, PO4 and F imply the role of regional flow and denitrification in the groundwater. Results concluded that proper management plan is necessary to protect the shallow aquifer in the RSB since shallow aquifer pumping is less expensive than the deeper one.

Comparative performance evaluation of multi-metal resistant fungal strains for simultaneous removal of multiple hazardous metals.

In the present study, five fungal strains viz., Aspergillus terreus AML02, Paecilomyces fumosoroseus 4099, Beauveria bassiana 4580, Aspergillus terreus PD-17, Aspergillus fumigatus PD-18, were screened for simultaneous multimetal removal. Highest metal tolerance index for each individual metal viz., Cd, Cr, Cu, Ni, Pb and Zn (500mg/L) was recorded for A. fumigatus for the metals (Cd, 0.72; Cu, 0.72; Pb, 1.02; Zn, 0.94) followed by B. bassiana for the metals (Cd, 0.56; Cu, 0.14; Ni, 0.29; Zn, 0.85). Next, the strains were exposed to multiple metal mixture (Cd, Cr, Cu, Ni, Pb and Zn) of various concentrations (6, 12, 18, 30mg/L). Compared to other strains, B. bassiana and A. fumigatus had higher cube root growth (k) constants indicating their better adaptability to multi metal stress. After 72h, multimetal accumulation potential of B. bassiana (26.94±0.07mg/L) and A. fumigatus (27.59±0.09mg/L) were higher than the other strains at initial multimetal concentration of 30mg/L. However, considering the post treatment concentrations of individual metals in multimetal mixture (at all the tested concentrations), A. fumigatus demonstrated exceptional performance and could bring down the concentrations of Cd, Cu, Ni, Pb and Zn below the threshold level for irrigation prescribed by Food and Agriculture Organization (FAO).

Cyclin-Dependent Kinase Inhibitors for the Treatment of Breast Cancer: Past, Present, and Future.

Treatment of metastatic breast cancer (MBC) that is resistant to endocrine therapy presents a significant clinical challenge. The well-known role of cell cycle dysregulation in these patients is partly mediated by cyclin-dependent kinase (CDK) activity. Specific cyclin and CDK complexes regulate cell cycle progression by managing the transition through the cell cycle, and inhibition of CDKs represents an important target for novel agents. First-generation CDK inhibitors (e.g., flavopiridol) were relatively nonselective and had an unacceptable toxicity profile in early trials. Second-generation CDK inhibitors were designed to target the CDK4 and CDK6 (CDK4/6) pathway and have shown promising clinical activity with an acceptable toxicity profile in patients with MBC. Palbociclib is a first-in-class CDK4/6 inhibitor that was granted accelerated U.S. Food and Drug Administration approval in combination with letrozole for the treatment of MBC in the first-line setting (February 2015) as well as in combination with fulvestrant for MBC that had progressed on previous endocrine therapy (February 2016). Other CDK4/6 inhibitors, including ribociclib and abemaciclib, are under investigation as monotherapy and in combination with endocrine or anti-human epidermal growth receptor 2 therapy for the treatment of MBC. Ongoing clinical trials should provide additional information to guide the appropriate use of these agents and identify patient populations that could derive the most benefit.

Cost-benefit assessment of using electronic health records data for clinical research versus current practices: Contribution of the Electronic Health Records for Clinical Research (EHR4CR) European Project.

INTRODUCTION: The widespread adoption of electronic health records (EHR) provides a new opportunity to improve the efficiency of clinical research. The European EHR4CR (Electronic Health Records for Clinical Research) 4-year project has developed an innovative technological platform to enable the re-use of EHR data for clinical research. The objective of this cost-benefit assessment (CBA) is to assess the value of EHR4CR solutions compared to current practices, from the perspective of sponsors of clinical trials. MATERIALS AND METHODS: A CBA model was developed using an advanced modeling approach. The costs of performing three clinical research scenarios (S) applied to a hypothetical Phase II or III oncology clinical trial workflow (reference case) were estimated under current and EHR4CR conditions, namely protocol feasibility assessment (S1), patient identification for recruitment (S2), and clinical study execution (S3). The potential benefits were calculated considering that the estimated reduction in actual person-time and costs for performing EHR4CR S1, S2, and S3 would accelerate time to market (TTM). Probabilistic sensitivity analyses using Monte Carlo simulations were conducted to manage uncertainty. RESULTS: Should the estimated efficiency gains achieved with the EHR4CR platform translate into faster TTM, the expected benefits for the global pharmaceutical oncology sector were estimated at €161.5m (S1), €45.7m (S2), €204.5m (S1+S2), €1906m (S3), and up to €2121.8m (S1+S2+S3) when the scenarios were used sequentially. CONCLUSIONS: The results suggest that optimizing clinical trial design and execution with the EHR4CR platform would generate substantial added value for pharmaceutical industry, as main sponsors of clinical trials in Europe, and beyond.

Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy.

Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, ß = -0.06, p = 1.1 x 10(-7)). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 x 10(-7). Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.

Assessment of Yamuna and associated drains used for irrigation in rural and peri-urban settings of Delhi NCR.

The present study assessed the quality of Yamuna River and the Najafgarh drain water for irrigational purposes in the Delhi region in terms of spatial variations in the physicochemical characteristics as well as heavy metal concentrations. The monitoring was done for the period July 2012-August 2013 representing pre-monsoon, monsoon, and post-monsoon sessions and considering six physicochemical parameters. Heavy metals such as cadmium, chromium, copper, nickel, zinc, and lead have been found in the river due to rampant discharge of industrial effluents into the river. The mean metal concentrations in the 15 sampling sites were in the range of (mg L(-1)) 0.02-0.64 (Cu), 0-0.42 (Cr), 0.13-2.22(Zn), 0.03-0.27 (Pb), 0-0.07 (Cd), and 0.01-0.13 (Ni). Multivariate statistics (PCA and HCA) were used to identify the possible sources of metal contamination and to examine the spatial changes in the Yamuna River as well as in the Najafgarh drain. This study reveals the occurrence of mean Cd concentration above the safe limit at Palla, Christian Ashram and Jagatpur of the Yamuna river while Punjabi Bagh of the Najafgarh drain necessitate treatment in terms of heavy metals such as Cd, Cu, Cr, Ni, Pb, and Zn before it could be rendered useful for irrigation.

Customer loyalty among daily disposable contact lens wearers.

BACKGROUND: Optometric practices offer contact lenses as cash sale items or as part of monthly payment plans. With the contact lens market becoming increasingly competitive, patients are opting to purchase lenses from supermarkets and Internet suppliers. Monthly payment plans are often implemented to improve loyalty. This study aimed to compare behavioural loyalty between monthly payment plan members and non-members. METHODS: BBR Optometry Ltd offers a monthly payment plan (Eyelife™) to their contact lens wearers. A retrospective audit of 38 Eyelife™ members (mean±SD: 42.7±15.0 years) and 30 non-members (mean±SD: 40.8±16.7 years) was conducted. Revenue and profits generated, service uptake and product sales between the two groups were compared over a fixed period of 18 months. RESULTS: Eyelife™ members generated significantly higher professional fee revenue (P<0.001), £153.96 compared to £83.50, and profits (P<0.001). Eyelife™ members had a higher uptake of eye examinations (P<0.001). The 2 groups demonstrated no significant difference in spectacle sales by volume (P=0.790) or value (P=0.369). There were also no significant differences in contact lens revenue (P=0.337), although Eyelife™ members did receive a discount. The Eyelife™ group incurred higher contact lens costs (P=0.037), due to a greater volume of contact lens purchases, 986 units compared to 582. CONCLUSIONS: Monthly payment plans improve loyalty among contact lens wearers, particularly service uptake and volume of lens purchases. Additionally the greater professional fees generated, render monthly payment plans an attractive business model and practice builder.