Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

X-ray Diffraction of Water in Polyvinylpyrrolidone.

PVP is a hydrophilic polymer commonly used as an excipient in pharmaceutical formulations. Here we have performed time-resolved high-energy X-ray scattering experiments on pellets of PVP at different humidity conditions for 1-2 days. A two-phase exponential decay in water sorption is found with a peak in the differential pair distribution function at 2.85 Å, which is attributed to the average (hydrogen bonded) carbonyl oxygen-water oxygen distance. Additional scattering measurements on powders with fixed compositions ranging from 2 to 12.3 wt % H2O were modeled with Empirical Potential Structure Refinement (EPSR). The models reveal approximately linear relations between the carbonyl oxygen-water oxygen coordination number (nOC-OW) and the water oxygen-water oxygen coordination number (nOW-OW) versus water content in PVP. A stronger preference for water-water hydrogen bonding over carbonyl-water bonding is found. At all the concentrations studied the majority of water molecules were found to be randomly isolated, but a wide distribution of coordination environments of water molecules is found within the PVP polymer strands at the highest concentrations. Overall, the EPSR models indicate a continuous evolution in structure versus water content with nOW-OW=1 occurring at ∼12 wt % H2O, i.e., the composition where, on average, each water molecule is surrounded by one other water molecule.

RNA- and ATAC-sequencing Reveals a Unique CD83+ Microglial Population Focally Depleted in Parkinson's Disease.

All brain areas affected in Parkinson's disease (PD) show an abundance of microglia with an activated morphology together with increased expression of pro-inflammatory cytokines, suggesting that neuroinflammation may contribute to the neurodegenerative process in this common and incurable disorder. We applied a single nucleus RNA- and ATAC-sequencing approach using the 10x Genomics Chromium platform to postmortem PD samples to investigate microglial heterogeneity in PD. We created a multiomic dataset using substantia nigra (SN) tissues from 19 PD donors and 14 non-PD controls (NPCs), as well as three other brain regions from the PD donors which are differentially affected in this disease: the ventral tegmental area (VTA), substantia inominata (SI), and hypothalamus (HypoTs). We identified thirteen microglial subpopulations within these tissues as well as a perivascular macrophage and a monocyte population, of which we characterized the transcriptional and chromatin repertoires. Using this data, we investigated whether these microglial subpopulations have any association with PD and whether they have regional specificity. We uncovered several changes in microglial subpopulations in PD, which appear to parallel the magnitude of neurodegeneration across these four selected brain regions. Specifically, we identified that inflammatory microglia in PD are more prevalent in the SN and differentially express PD-associated markers. Our analysis revealed the depletion of a CD83 and HIF1A- expressing microglial subpopulation, specifically in the SN in PD, that has a unique chromatin signature compared to other microglial subpopulations. Interestingly, this microglial subpopulation has regional specificity to the brainstem in non-disease tissues. Furthermore, it is highly enriched for transcripts of proteins involved in antigen presentation and heat-shock proteins, and its depletion in the PD SN may have implications for neuronal vulnerability in disease.

Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk.

The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase ~50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 copy number. Population studies, including USA-based cohorts, showed distinct KIV-2 CN, distributions for European-, African-, and Hispanic-American populations and further underscored the limitations of SNV predictors. We demonstrate that the CN estimates correlate significantly with the available Lp(a) protein levels and that phasing is highly important.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

OBJECTIVES: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. DESIGN: Economic evaluation from healthcare system and societal perspectives. SETTING: Ten diverse urban clinics in India and Pakistan. PARTICIPANTS: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. INTERVENTION: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). RESULTS: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. CONCLUSIONS: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

The prevalence of Schmorl's nodes in osteoporotic vs normal patients: a Middle Eastern population study.

The study was conducted to establish the association of Schmorl's nodes and osteoporosis in a Middle Eastern cohort. The prevalence of SN in this sample was 41.1%. It was most frequent in the lumbar spine typically solitary central lesions. Over 88% Schmorl's node cases were osteoporotic/osteopenic and only 11.6% normal. INTRODUCTION: This study aims to identify the prevalence of Schmorl's nodes (SNs) in a cohort of Omani nationals, and also to determine any relation between osteoporosis and Schmorl's nodes. METHODS: This retrospective observational study was conducted on Omani nationals. One thousand three hundred and forty-eight DEXA scan patients were included. Of these, 545 patients had complete X-rays and MRI scans that would help determine the SN status. The X-rays and sagittal, coronal, and axial T2-weighted MR images were used to identify the presence and exact location of the Schmorl nodes by one orthopedic trainee and confirmed by the senior author. The correlation of each parameter with the presence of SN was analyzed by the independent-samples T test and one-way ANOVA. RESULTS: The overall prevalence of SN in this population sample appeared to be 41.1%. Over 88% of the SN-positive cases were either osteopenic or frankly osteoporotic by the WHO definition. Vast majority of SNs (87.1%) occurred in the lumbar spine and were central in location and mostly solitary. Statistical analysis of the data revealed significant correlation between osteopenia or osteoporosis and the presence of SNs. CONCLUSIONS: The prevalence of SN in the sample of Omanis studied was 41.1% and was most frequently seen in older men in the lumbar spine. It is strongly associated with osteoporosis/osteopenia (88.4%) and frequently presents as solitary central lesions.

Topological phonon-polariton funneling in midinfrared metasurfaces.

Topological photonics offers enhanced control over electromagnetic fields by providing a platform for robust trapping and guiding of topological states of light. By combining the strong coupling between topological photons with phonons in hexagonal boron nitride (hBN), we demonstrate a platform to control and guide hybrid states of light and lattice vibrations. The observed topological edge states of phonon-polaritons are found to carry nonzero angular momentum locked to their propagation direction, which enables their robust transport. Thus, these topological quasiparticles enable the funneling of infrared phonons mediated by helical infrared photons along arbitrary pathways and across sharp bends, thereby offering opportunities for applications ranging from Raman and vibrational spectroscopy with structured phonon-polaritons to directional heat dissipation.

FRAX-based osteoporosis treatment guidelines for resource-poor settings in India.

Using the FRAX® model for India, thresholds for osteoporosis evaluation and treatment without bone mineral density measurement were derived and were validated in a cohort of 300 patients. We suggest the use of this newer age and ethnic-specific FRAX®-derived thresholds for management of osteoporosis in India. PURPOSE: Our study aimed to formulate population-specific intervention thresholds for treatment of osteoporosis in India which can be used even without dual X-ray absorptiometry (DXA). METHODS: Using the FRAX® model for India, thresholds for different age groups for men and women were calculated without bone mineral density (BMD) measurement. The lower assessment threshold (LAT) was based on the 10-year probability of a major osteoporosis fracture (MOF) or hip fracture (HF) equivalent to patients without clinical risk factors. The intervention threshold (IT) was based on the 10-year probability equivalent to patients with fracture. The upper assessment threshold (UAT) was set at 1.2 times the IT. Probability-based thresholds for no intervention (LAT), treatment initiation (UAT) and BMD assessment (between LAT and UAT) were derived. The thresholds were validated in a cohort of 300 patients who were referred for BMD testing. RESULTS: Graphs for age, gender, BMI and ethnic-specific LAT, IT and UAT for MOF and HF are derived. In the validation cohort, BMD testing to initiate/defer treatment was required in only 32.3% patients. The intervention thresholds derived without BMD testing were valid in 98.7% patients. Use of National Osteoporosis Foundation (NOF) guidelines would have resulted in overtreatment in 56/300 (18.6%) patients. CONCLUSION: We suggest the use of this newer age and ethnic-specific FRAX®-derived thresholds for management of osteoporosis. Adopting these cut-offs will ensure that those requiring osteoporosis treatment will not be denied of it just because of lack of a DXA machine and will also help avoid overtreatment.

Oral Levothyroxine is an Effective Option for Myxedema Coma: A Single-Centre Experience.

INTRODUCTION: Myxedema coma is an endocrine emergency with a very high mortality rate. As per the American Thyroid Association, initial thyroid hormone replacement for myxedema coma should be intravenous levothyroxine (LT4). However, in India, the availability of intravenous LT4 is limited. Often, crushed LT4 tablets are given through the enteral route when parenteral therapy is unavailable. No data or protocol is available for the administration of oral LT4 in myxedema coma. The aim of this study was to assess the effectiveness of oral LT4 in patients diagnosed with myxedema coma and to formulate a protocol for oral LT4 that can be used to guide the treatment of patients when intravenous LT4 is unavailable. METHODS: This retrospective observational study included patients diagnosed with myxedema coma between January 2010 and December 2019. The diagnosis of myxedema coma was based on the diagnostic scoring system for myxedema coma proposed by Popoveniuc et al. [Endocr Pract. 2014 Aug;20(8):808-17]. Dosing of oral LT4 was decided as per our institutional protocol. RESULTS: Fourteen patients (11 males and 3 females) with a median age of 67.5 years (range 11-82) with myxedema coma were included. All patients had central nervous system manifestations, and sepsis was the most common precipitating factor. The median myxedema score was 72.5 (normal ≤25), and the median length of hospital stay was 12 days (range 3-18). The oral LT4 regimen consisted of a loading dose of 300-500 µg, followed by taper over the next 3-5 days. With this regimen, 13 patients survived, and only 1 patient died. CONCLUSION: Oral LT4 is an effective treatment option for myxedema coma when intravenous LT4 is unavailable.

Transfusion-associated anxiety: Recognised and overcome in an adolescent child.

A 12-year-old boy presented to our palliative care cancer clinic with Ewing Sarcoma and anaemia in failure. Transfusion reactions were noted during several blood transfusions, which manifested as acute onset of breathlessness, mild chest pain, sweating, general discomfort, increased heart rate, respiratory rate, and blood pressure. All the possible causes of transfusion reaction were ruled out, other than transfusion-associated anxiety resembling transfusion reaction. In this case, adequate reassurance, counselling about the blood transfusion, distraction techniques, and the visual technique of masking the blood bag with black polythene foil helped overcome the patient's anxiety during the blood transfusion, and was uneventful henceforth. Since transfusion-associated anxiety is not an established and well-studied aspect of transfusion medicine yet, there is a need to have high clinical suspicion to recognise, assess, and forthwith prevent any such transfusion reactions without any delay.

Tobacco use and exposure to second-hand smoke among high school students in Ernakulum district, Kerala: A cross-sectional study.

Objectives: Tobacco use and exposure to second-hand smoke (SHS) in the home setting are major health hazards for adolescents. The objectives of this study were to estimate tobacco use and exposure to SHS among high school students in Ernakulam district of Kerala, India, and to investigate associated factors. Study design: Cross-sectional study. Methods: A school-based cross-sectional study was carried out in 25 randomly selected high schools from 210 schools in the Ernakulam educational district of Kerala, India. The minimum calculated sample size for ever-use of tobacco and SHS exposure was determined to be 2500, with 95% confidence interval (CI) and 10% relative precision. Data were collected using a semi-structured, pre-tested questionnaire from 2585 high school students. Data analyses were performed using SPSS version 20. Results: The ever-use of tobacco was reported to be 3.9% (95% CI 3.16 to 4.54) and the mean age of the participants was 13.97 ± 0.77 years. One-fifth of participants had tried a tobacco product before the age of 10 years. SHS exposure at home was reported by one in every 5 respondents (20.3%). Male gender (adjusted odds ratio [aOR] 8.79; 95% CI 3.16, 24.53), presence of a family member who smokes within the home (aOR 4.28; 95% CI 2.58, 7.12), lack of awareness about the harmful effects of SHS exposure (aOR 2.47; 95% CI 1.41, 5.18) and having seen an advertisement or promotion at point of sale (aOR 2.16; 95% CI 1.29, 3.60) were found to be independent predictors for tobacco use.Participants with respiratory infections were three times more likely to have experienced SHS exposure at home (aOR 2.87; 95% CI 2.21, 3.74), there was an 86% protective effect of SHS exposure for participants with a father in a professional occupation compared with unskilled profession (aOR 0.14; 95% CI 0.02, 0.67; p < 0.15) and participants with ever-use of tobacco were two times more likely to have experienced SHS exposure at home (aOR 1.63; 95% CI 3.13, 8.98). Conclusions: SHS exposure in the home environment continues to be high. Urgent innovative measures are necessary for the implementation of tobacco smoke-free homes and to reduce tobacco use in this vulnerable population. Further studies are necessary to determine ways to reduce smoking within homes and to increase population awareness.

Do Biometric Readings Change Significantly over Time in Phakic Eyes? A Cohort Study.

Background: Precise biometric assessment is crucial in achieving desirable refractive outcomes following cataract surgery. The current evidence for longitudinal biometric changes is lacking. We have performed a cohort study of phakic patients undergoing cataract surgery to help demonstrate whether biometric parameters change over time. Methods: We performed a single-centre, historic cohort study of patients who attended a "two-stop" pre-assessment clinic for consideration of cataract surgery between November 2002 and March 2015. Data were collected retrospectively. Four biometric measurements were recorded: axial length, horizontal (K1) readings, vertical (K2) readings and dioptric power of lens (AR40). Patients were allocated to three groups according to the time interval between initial and latest biometric assessment: Group 1: up to 12 months; Group 2: 12-24 months; Group 3: over 24 months. Results: Data were obtained for 109 eyes from 62 patients. Mean patient age at first biometry was 78 (range: 49-95; S.D.:10). Thirty-eight patients (61.3%) were female. Paired t-tests were performed per biometric measurement per group. No statistically significant changes were observed in Group 1 (n = 9). In Group 2, a statistically significant change was observed in K1 readings (median change: -0.12 mm, range: -0.65 mm to 0.64 mm; P = .002). In Group 3, statistically significant changes were observed in K1 readings (median change: 0.06 mm, range: -0.59 mm to 1.29 mm, P = .03), K2 readings: (median change: 0.33 mm, range: -0.50 mm to 1.09 mm, P < .001) and no change in AR40 readings (median change: 0.00, range -2.00 to 3.00, P = .02). Conclusion: Statistically significant biometric changes were observed over time in this cohort. We recommend considering repeat biometric assessment in patients who have had an interval of longer than 24 months between initial biometric assessment and surgery for optimal refractive outcomes. Further research is required to identify more precisely when to expect changes in the various biometric parameters and which patient characteristics may contribute.

Neural correlates of cognitive variability in childhood autism and relation to heterogeneity in decision-making dynamics.

Heterogeneity in cognitive and academic abilities is a prominent feature of autism spectrum disorder (ASD), yet little is known about its underlying causes. Here we combine functional brain imaging during numerical problem-solving with hierarchical drift-diffusion models of behavior and standardized measures of numerical abilities to investigate neural mechanisms underlying cognitive variability in children with ASD, and their IQ-matched Typically Developing (TD) peers. Although the two groups showed similar levels of brain activation, the relation to individual abilities differed markedly in ventral temporal-occipital, parietal and prefrontal regions important for numerical cognition: children with ASD showed a positive correlation between functional brain activation and numerical abilities, whereas TD children showed the opposite pattern. Despite similar accuracy and response times, decision thresholds were significantly higher in the ASD group, suggesting greater evidence required for problem-solving. Critically, the relationship between individual abilities and engagement of prefrontal control systems anchored in the anterior insula was differentially moderated by decision threshold in subgroups of children with ASD. Our findings uncover novel cognitive and neural sources of variability in academically-relevant cognitive skills in ASD and suggest that multilevel measures and latent decision-making dynamics can aid in characterization of cognitive variability and heterogeneity in neurodevelopmental disorders.

Infectious diseases and antimicrobial prescribing: Online spaced education for junior doctors.

BACKGROUND: Inappropriate antimicrobial prescribing may harm patients and drive antimicrobial resistance. Junior doctors' knowledge of infectious diseases and antimicrobial prescribing is inadequate. Online spaced case-based learning can improve knowledge. OBJECTIVE: To develop infectious diseases and antimicrobial prescribing course content for online spaced education and assess its effectiveness and feasibility for junior doctors. METHODS: Infectious diseases and antimicrobial course content was developed for an online spaced education platform (Qstream Inc., Burlington, MA). Junior doctors (postgraduate years 1-3) at two tertiary teaching hospitals in Sydney participated in the study. Course content was provided with Qstream at one hospital and at the other hospital via two face-to-face (FTF) tutorials from August to October 2017. Knowledge and self-confidence were compared before and after training within and between both cohorts. RESULTS: Participation in the course was higher in the Qstream cohort with 48/127 (37.8%) completing the course compared with 44/110 (40%) attending one or both FTF sessions, of whom 22/110 (20%) attended both. Improvement in mean knowledge score from 69.7% to 81.5% in the Qstream cohort was significantly greater than the FTF cohort's minimal improvement from 67.6% to 67.9% (95% CI 2.79-20.33; P=0.01). In the Qstream cohort mean confidence rating (0-10) improvement from 5.14 to 6.55 was greater than the FTF group improvement from 5.37 to 5.85 (95% CI 0.132-1.171; P=0.02). Qstream feedback was very positive. CONCLUSIONS: Online spaced education in infectious diseases and antimicrobial prescribing was feasible, acceptable and effective for junior doctors. It has potential to reduce inappropriate antimicrobial prescribing and warrants further investigation.

The Hernia 'CAMP' model: a collaborative action to maximise productivity within the NHS.

BACKGROUND: An ever-growing and long surgical waiting list is a challenge within the NHS. Long waiting times can result in complications of the condition with more challenging operations and additional procedures. All of which implies reduced quality of life for patients and increased strain on NHS finances. On an average there are about 160 patients on the waiting list for groin hernia surgeries, with over a half of them waiting more than 30 weeks. Three patients every year breach the 52 weeks timeline, flagging a never event, with negative implications for the trust. METHODS: The Hernia CAMP model was proposed to improve productivity and enhance patient experience. It helped create a pathway with experienced non-consultant surgeons, stepping up to free up consultants to attend to the pressing cancer and complex cases. This dedicated pathway, improved the patient experience and staff team-spirit too. RESULTS: The Hernia CAMP resulted in a 40% improvement in efficiency. With better ratio per list/session, it makes care more cost-effective. It also improved the work environment amongst staff and rapport with patients. The patient-peer support and greater involvement meant better overall experience too. This supportive environment also has the potential for theme-based learning and training. CONCLUSIONS: The Hernia 'CAMP' is a transferable and adaptable model. It impacts not just long waiting lists, but also improves productivity with definite cost benefits, teambuilding, patient experience and creates a great opportunity to train too.

Fluorescence Emission Triggered by Radioactive ß decay in Optimized Hyperbolic Cavities.

Luminescence arising from ß -decay of radiotracers has garnered much interest recently as a viable in-vivo imaging technique. The emitted Cerenkov radiation can be directly detected by high sensitivity cameras or used to excite highly efficient fluorescent dyes. Here, we investigate the enhancement of visible and infrared emission driven by ß -decay of radioisotopes in the presence of a hyperbolic nanocavity. By means of a transfer matrix approach, we obtain quasi-analytic expressions for the fluorescence enhancement factor at the dielectric core of the metalodielectric cavity, reporting a hundred-fold amplification in periodic structures. A particle swarm optimization of the layered shell geometry reveals that up to a ten-thousand-fold enhancement is possible thanks to the hybridization and spectral overlapping of whispering-gallery and localized-plasmon modes. Our findings may find application in nuclear-optical medical imaging, as they provide a strategy for the exploitation of highly energetic gamma rays, Cerenkov luminescence, and visible and near-infrared fluorescence through the same nanotracer.

Effect of a multicomponent intervention on achievement and improvements in quality-of-care indices among people with Type 2 diabetes in South Asia: the CARRS trial.

AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.

Rationale and protocol for estimating the economic value of a multicomponent quality improvement strategy for diabetes care in South Asia.

BACKGROUND: Economic dimensions of implementing quality improvement for diabetes care are understudied worldwide. We describe the economic evaluation protocol within a randomised controlled trial that tested a multi-component quality improvement (QI) strategy for individuals with poorly-controlled type 2 diabetes in South Asia. METHODS/DESIGN: This economic evaluation of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomised trial involved 1146 people with poorly-controlled type 2 diabetes receiving care at 10 diverse diabetes clinics across India and Pakistan. The economic evaluation comprises both a within-trial cost-effectiveness analysis (mean 2.5 years follow up) and a microsimulation model-based cost-utility analysis (life-time horizon). Effectiveness measures include multiple risk factor control (achieving HbA1c < 7% and blood pressure < 130/80 mmHg and/or LDL-cholesterol< 100 mg/dl), and patient reported outcomes including quality adjusted life years (QALYs) measured by EQ-5D-3 L, hospitalizations, and diabetes related complications at the trial end. Cost measures include direct medical and non-medical costs relevant to outpatient care (consultation fee, medicines, laboratory tests, supplies, food, and escort/accompanying person costs, transport) and inpatient care (hospitalization, transport, and accompanying person costs) of the intervention compared to usual diabetes care. Patient, healthcare system, and societal perspectives will be applied for costing. Both cost and health effects will be discounted at 3% per year for within trial cost-effectiveness analysis over 2.5 years and decision modelling analysis over a lifetime horizon. Outcomes will be reported as the incremental cost-effectiveness ratios (ICER) to achieve multiple risk factor control, avoid diabetes-related complications, or QALYs gained against varying levels of willingness to pay threshold values. Sensitivity analyses will be performed to assess uncertainties around ICER estimates by varying costs (95% CIs) across public vs. private settings and using conservative estimates of effect size (95% CIs) for multiple risk factor control. Costs will be reported in US$ 2018. DISCUSSION: We hypothesize that the additional upfront costs of delivering the intervention will be counterbalanced by improvements in clinical outcomes and patient-reported outcomes, thereby rendering this multi-component QI intervention cost-effective in resource constrained South Asian settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01212328.