A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach.

AIMS: To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS: We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS: The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS: We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.

[Trisomy 18: how lethal is 'lethal'?] / Trisomie 18: hoe lethaal is 'lethaal'?

Should active treatment be available for children with trisomy 18? In the Netherlands, trisomy 18 is described as a lethal condition leading to death during or immediately after birth. The Dutch course of action for trisomy 18 is termination of pregnancy, almost without exception, or passive treatment without medical interventions. But that approach might be outdated. We present a case that inspired physicians and parents to rethink the perception of trisomy 18.

Utility of the Morisky Medication Adherence Scale in gout: a prospective study.

BACKGROUND: The outcomes of any chronic illness often depend on patients' adherence with their treatment. A tool is lacking to assess adherence in gout that is standardized, allows real-time feedback, and is easy to understand. OBJECTIVE: We set out to evaluate the utility of the 8-item Morisky Medication Adherence Scale (MMAS-8) in monitoring medication adherence in a multiethnic Asian gout cohort on urate-lowering therapy (ULT). METHODS: This cohort study recruited patients with gout where baseline and 6-monthly clinical data, self-report of adherence, and health status by Gout Impact Scale (GIS) and EuroQoL-5 dimension 3 levels were collected. Those who received at least 9 months of ULT were analyzed. Convergent and construct validities of MMAS-8 were evaluated against medication possession ratio (MPR) and known groups, clinical outcomes, and patient-reported outcomes. Internal consistency and test-retest reliability were assessed using Cronbach's alpha and intraclass correlation coefficient (ICC), respectively. RESULTS: Of 91 patients, 92.3% were male, 72.5% Chinese with mean age 53.5 years. MMAS-8 (mean 6.17) and MPR (mean 96.3%) were poorly correlated (r=0.069, P=0.521). MMAS-8 did not differ between those who did or did not achieve target serum urate (SU) <360 µmol/L (P=0.852); or among those whose SU improved, stagnated, or worsened during follow-up (P=0.777). Adherence was associated with age (ß=0.256, P=0.015) and education level (P=0.011) but not comorbidities, polypharmacy, or flare frequency. Concerns for medication side effects and anxiety or depression were associated with lower MMAS-8 (P<0.005). Internal consistency was acceptable (α=0.725) and test-retest reliability was satisfactory (ICC =0.70, 95% confidence interval [CI] 0.36-0.88). CONCLUSION: MMAS-8 had limited construct validity in assessing medication adherence to ULT in our gout patients. Nevertheless, it identified patients bothered or worried about ULT side effects, and those with underlying anxiety or depression, for whom targeted education and coping support may be useful.

Humanistic and economic outcomes of pharmacist-provided medication review in the community-dwelling elderly: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Recent reviews have shown that pharmacist-provided medication review in the elderly can improve clinical outcomes and reduce medication discrepancies compared with usual care. However, none determined whether these translate to improved humanistic and economic outcomes. This review sought to evaluate the effects of medication review on health-related quality of life (HRQoL) and healthcare costs in the elderly. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane library for studies published in English from inception to 31 August 2015 was conducted. The review included studies lasting at least 3 months that randomly assigned community-dwelling participants aged at least 65 years to receive either pharmacist-provided medication review or usual care. Studies set in nursing homes were excluded. RESULTS AND DISCUSSION: The review identified 25 studies that included 15 341 participants and lasted between 3 and 36 months. Twenty and 13 studies reported HRQoL and economic outcomes, respectively. Overall, there was no significant difference in HRQoL and healthcare costs between pharmacist-provided medication review and usual care. Meta-analysis of studies that reported the 36-item Short-Form Health Survey found significant differences in favour of usual care in the body pain (mean difference: 2·94, 95% CI: 0·54-5·34, P = 0·02) and general health perception (mean difference: 1·83, 95% CI: 0·16-3·50, P = 0·03) domains, whereas there were no significant differences in other domains. Meta-analysis of the EuroQol-5D utility (mean difference: -0·01, 95% CI: -0·02-0·01, P = 0·57) and visual analogue scale (mean difference: 0·01, 95% CI: -3·24-3·26, P = 1·00) found no significant differences. Costs of hospitalization, medication and other healthcare resources consumed were similar between groups. WHAT IS NEW AND CONCLUSION: Humanistic and economic outcomes of pharmacist-provided medication review were largely similar to those of usual care. Further research using more robust methodology is needed to determine whether improved medication management can improve HRQoL and reduce healthcare costs. Careful thought should be given to capturing relevant outcomes that reflect the potential benefits of this intervention.

A scoring model for predicting survival following primary tumour resection in stage IV colorectal cancer patients with unresectable metastasis.

BACKGROUND: Stage IV colorectal cancer patients with unresectable metastasis who undergo elective primary tumour resection experience heterogeneous post-operative survival. We aimed to develop a scoring model for predicting post-operative survival using pre-operative variables to identify patients who are least likely to experience extended survival following the procedure. METHODS: Survival data were collected from stage IV colorectal cancer patients who had undergone elective primary tumour resection between January 1999 and December 2007. Coefficients of significant covariates from the multivariate Cox regression model were used to compute individual survival scores to classify patients into three prognostic groups. A survival function was derived for each group via Kaplan-Meier estimation. Internal validation was performed. RESULTS: Advanced age (hazard ratio, HR 1.43 (1.16-1.78)); poorly differentiated tumour (HR 2.72 (1.49-5.04)); metastasis to liver (HR 1.76 (1.33-2.33)), lung (HR 1.37 (1.10-1.71)) and bone (HR 2.08 ((1.16-3.71)); carcinomatosis (HR 1.68 (1.30-2.16)); hypoalbuminaemia (HR 1.30 (1.04-1.61) and elevated carcinoembryonic antigen levels (HR 1.89 (1.49-2.39)) significantly shorten post-operative survival. The scoring model separated patients into three prognostic groups with distinct median survival lengths of 4.8, 12.4 and 18.6 months (p < 0.0001). Internal validation revealed a concordance probability estimate of 0.65 and a time-dependent area under receiver operating curve of 0.75 at 6 months. Temporal split-sample validation implied good local generalizability to future patient populations (p < 0.0001). CONCLUSION: Predicting survival following elective primary tumour resection using pre-operative variables has been demonstrated with the scoring model developed. Model-based survival prognostication can support clinical decisions on elective primary tumour resection eligibility.

Understanding domains of health-related quality of life concerns of Singapore Chinese patients with advanced cancer: a qualitative analysis.

PURPOSE: Quality of life concerns in patients with advanced diseases might be different from other patients and are shaped by sociocultural context. The objective of this qualitative study was to identify domains and themes of health-related quality of life (HRQoL) that Chinese patients with advanced cancer in Singapore considered relevant and important. METHODS: English- and Chinese-speaking patients with advanced solid cancer were recruited from a tertiary cancer center and a community-based hospice for in-depth interview or focused group discussion. Thematic analysis was used to identify subthemes, themes, and domains from the transcripts. RESULTS: Forty-six ethnic Chinese (aged 26-86, 48% male) participated in the study. Six domains of HRQoL concerns were identified: pain and suffering, physical health, social health, mental health, financial well-being, and spiritual health. Pain and suffering are not limited to the physical domain, reflecting the multidimensional nature of this concept. Pain and suffering must also be understood within the cultural context. Healthcare relations (i.e., social health), existential well-being and religious well-being (i.e., spiritual health), and suffering (i.e., pain and suffering) are not fully captured in the existing HRQoL instruments. In addition, financial issues and the practice of secrecy in interpersonal relationships emerged as unique features possibly arising from our sociocultural context and healthcare financing landscape. CONCLUSION: Socioculturally specific issues not measured by the existing HRQoL instruments for use in patients with advanced cancers or terminal diseases were found in our study. These are non-physical pain and suffering, meaning of illness, meaning of death, financial issues, and practice of secrecy in interpersonal relationships.

Effect of the CYP3A5 and ABCB1 genotype on exposure, clinical response and manifestation of toxicities from sunitinib in Asian patients.

The objective of this study was to determine the effect of the CYP3A5 and ATP binding cassette subfamily B member 1 (ABCB1) single-nucleotide polymorphisms on the disposition of sunitinib and SU12662, on clinical response, and on the manifestation of toxicities in Asian metastatic renal cell carcinoma patients. At week 4 of each treatment cycle, toxicities and plasma steady-state levels were assessed. Clinical response was assessed after two cycles. Genotyping was performed by using the PCR restriction fragment length polymorphism method. The CC genotype for ABCB1 was associated with a higher sunitinib exposure (76.81 vs 56.55 ng ml(-1), P=0.03), higher risk of all-grade rash (RR 3.00, 95% CI 1.17-7.67) and mucositis (RR 1.60, 95% CI 1.10-2.34) and disease progression than compared with the CT/TT genotype. There was a lack of association observed between the CYP3A5 polymorphism and exposure, response and toxicities. The polymorphism of ABCB1 (C3435T) has an important role in the manifestation of toxicities and drug exposure, but not polymorphism of CYP3A5.

Quantifying the natural history of breast cancer.

BACKGROUND: Natural history models of breast cancer progression provide an opportunity to evaluate and identify optimal screening scenarios. This paper describes a detailed Markov model characterising breast cancer tumour progression. METHODS: Breast cancer is modelled by a 13-state continuous-time Markov model. The model differentiates between indolent and aggressive ductal carcinomas in situ tumours, and aggressive tumours of different sizes. We compared such aggressive cancers, that is, which are non-indolent, to those which are non-growing and regressing. Model input parameters and structure were informed by the 1978-1984 Ostergotland county breast screening randomised controlled trial. Overlaid on the natural history model is the effect of screening on diagnosis. Parameters were estimated using Bayesian methods. Markov chain Monte Carlo integration was used to sample the resulting posterior distribution. RESULTS: The breast cancer incidence rate in the Ostergotland population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length-biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI: 3-16 years), whereas aggressive ductal carcinomas in situ took around half a month (95% CI: 0-1 month) to progress to the invasive ≤10 mm state. CONCLUSION: These tumour progression rate estimates may facilitate future work analysing cost-effectiveness and quality-adjusted life years for various screening strategies.

High-fidelity readout and control of a nuclear spin qubit in silicon.

Detection of nuclear spin precession is critical for a wide range of scientific techniques that have applications in diverse fields including analytical chemistry, materials science, medicine and biology. Fundamentally, it is possible because of the extreme isolation of nuclear spins from their environment. This isolation also makes single nuclear spins desirable for quantum-information processing, as shown by pioneering studies on nitrogen-vacancy centres in diamond. The nuclear spin of a (31)P donor in silicon is very promising as a quantum bit: bulk measurements indicate that it has excellent coherence times and silicon is the dominant material in the microelectronics industry. Here we demonstrate electrical detection and coherent manipulation of a single (31)P nuclear spin qubit with sufficiently high fidelities for fault-tolerant quantum computing. By integrating single-shot readout of the electron spin with on-chip electron spin resonance, we demonstrate quantum non-demolition and electrical single-shot readout of the nuclear spin with a readout fidelity higher than 99.8 percent-the highest so far reported for any solid-state qubit. The single nuclear spin is then operated as a qubit by applying coherent radio-frequency pulses. For an ionized (31)P donor, we find a nuclear spin coherence time of 60 milliseconds and a one-qubit gate control fidelity exceeding 98 percent. These results demonstrate that the dominant technology of modern electronics can be adapted to host a complete electrical measurement and control platform for nuclear-spin-based quantum-information processing.

Predicting preference-based SF-6D index scores from the SF-8 health survey.

PURPOSE: To develop and test functions for predicting the preference-based SF-6D index scores from the SF-8 health survey. METHODS: This study was a secondary analysis of data collected in a population health survey in which respondents (n = 7,529) completed both the SF-36 and the SF-8 questionnaires. We examined seven ordinary least-square estimators for their performance in predicting SF-6D scores from the SF-8 at both the individual and the group levels. RESULTS: In general, all functions performed similarly well in predicting SF-6D scores, and the predictions at the group level were better than predictions at the individual level. At the individual level, 42.5-51.5% of prediction errors were smaller than the minimally important difference (MID) of the SF-6D scores, depending on the function specifications, while almost all prediction errors of the tested functions were smaller than the MID of SF-6D at the group level. At both individual and group levels, the tested functions predicted lower than actual scores at the higher end of the SF-6D scale. CONCLUSIONS: Our study developed functions to generate preference-based SF-6D index scores from the SF-8 health survey, the first of its kind. Further research is needed to evaluate the performance and validity of the prediction functions.

Associations between complications and health-related quality of life in individuals with diabetes.

OBJECTIVE: Type 2 diabetes and associated complications adversely affect health-related quality of life (HRQoL). However, it is unclear whether different complications have the same or different associations with HRQoL. We examined associations between retinopathy, nephropathy, peripheral neuropathy (microvascular), coronary heart disease, stroke and peripheral arterial disease (macrovascular) in diabetes and HRQoL. DESIGN: This study was a follow-up examination between 2004 and 2007 of participants from four previous cross-sectional population-based studies in Singapore. METHODS: Health-related quality of life was assessed through self-administered SF-36 health survey version 2. Diabetes and complications status were assessed through self-report, clinical and laboratory examinations. About 2601 individuals, 2205 healthy and 396 with diabetes, were studied. RESULTS: Lower physical component scores (PCS) were associated with microvascular (2.96 points, P < 0.001) and both macro- and microvascular complications (4.67 points, P < 0.001), but not diabetes alone. Coronary heart disease (3.86 points, P = 0.007), peripheral neuropathy (11.46 points, P < 0.001) and severe retinopathy (4.46 points, P < 0.001) were associated with lower PCS. The greatest reduction in scores was seen in peripheral neuropathy. CONCLUSIONS: Quality of life in patients with diabetes is affected mainly by presence of complications, and not diabetes per se. Peripheral neuropathy was associated with the greatest reduction in quality of life. Improved management to prevent or delay onset of complications may reduce the effect on quality of life in patients with diabetes.

Estimating the lifetime economic burden of Parkinson's disease in Singapore.

BACKGROUND AND PURPOSE: We aimed to estimate the lifetime cost of Parkinson's disease (PD) from the societal perspective. METHODS: A convenience sample of English or Chinese-speaking patients with PD was recruited from a PD and Movement Disorders Centre in Singapore to complete a financial burden questionnaire. Sociodemographic and clinical data were retrieved from hospital databases. Markov cohort model analysis was performed (cycle length, 1-year; duration, death or reached 100 years old). Patients were assumed to progress from one Markov state to the next state or death without skipping states or regressing. All model parameters were based on published local data. RESULTS: In 195 patients with PD (median age: 68.9, male: 51.8%), the simulated lifetime cost of PD was Singapore Dollar (SGD) 60,487 (EUR purchasing power parity 56,253) per patient. Direct medical, non-medical and indirect cost accounted for 18.8%, 12.8% and 68.4% of total lifetime cost, respectively. The top three components of total lifetime cost were productivity losses (67.6%), pharmacotherapy (11.4%) and home care (8.7%). One-way sensitivity analysis and probabilistic sensitivity analyses revealed that estimates were sensitive to cost at H&Y stage 1, 2 and 2.5 and productivity losses. CONCLUSIONS: The lifetime cost of PD is evaluated for the first time. This cost is substantial and comparable to the lifetime cost of intracerebral haemorrhage in at least one study. Our study identified several priority areas for research and policy formulation: reducing productivity losses, reducing cost of pharmacotherapy, avoiding hospitalization and reducing home care cost.

A single-atom electron spin qubit in silicon.

A single atom is the prototypical quantum system, and a natural candidate for a quantum bit, or qubit--the elementary unit of a quantum computer. Atoms have been successfully used to store and process quantum information in electromagnetic traps, as well as in diamond through the use of the nitrogen-vacancy-centre point defect. Solid-state electrical devices possess great potential to scale up such demonstrations from few-qubit control to larger-scale quantum processors. Coherent control of spin qubits has been achieved in lithographically defined double quantum dots in both GaAs (refs 3-5) and Si (ref. 6). However, it is a formidable challenge to combine the electrical measurement capabilities of engineered nanostructures with the benefits inherent in atomic spin qubits. Here we demonstrate the coherent manipulation of an individual electron spin qubit bound to a phosphorus donor atom in natural silicon, measured electrically via single-shot read-out. We use electron spin resonance to drive Rabi oscillations, and a Hahn echo pulse sequence reveals a spin coherence time exceeding 200 µs. This time should be even longer in isotopically enriched (28)Si samples. Combined with a device architecture that is compatible with modern integrated circuit technology, the electron spin of a single phosphorus atom in silicon should be an excellent platform on which to build a scalable quantum computer.

Prenatal diagnosis of trisomy 9.

We present a foetus affected by trisomy 9, a rare chromosomal disorder, which was diagnosed in a low-risk patient during the first trimester of pregnancy. The finding of multiple structural foetal anomalies at the first trimester screening prompted chorionic villus sampling. Evaluation of the quantitative fluorescent polymerase chain reaction was normal, but the final karyotype result revealed a diagnosis of trisomy 9. First trimester screening for detection of foetal anomalies is highly effective. Although rapid molecular methods are available for prenatal diagnosis of common autosomal and sex chromosome aneuploidies, it is essential to obtain a full karyotype in order to exclude the less commonly encountered chromosomal abnormalities.

A highly phase-stable differential detector amplifier for magnetic induction tomography.

Magnetic induction tomography (MIT) has been proposed for the detection of cerebral oedema and haemorrhagic stroke. Achieving the required phase measurement precision for these applications is however a major technical challenge. A critical component within an MIT system is the detector amplifier and for this role an ultra-phase-stable, low noise instrumentation amplifier has been developed. The design of the amplifier is described and (i) the results of simulations and measurements of the amplifiers phase stability versus temperature and (ii) measurements of the phase noise and drift performance of the amplifier within a single-channel magnetic induction spectroscopy system are provided and discussed. For a 10 MHz signal the amplifier, with a gain of 21, displayed an average change in the measured phase of its output of just -0.1 ± 0.6 m° °C(-1) as the ambient temperature was varied between 35 and 50 °C, demonstrating a level of phase stability approaching that required for potential biomedical applications such as the detection of cerebral haemorrhage.

Economic burden of Parkinson's disease in Singapore.

BACKGROUND: This study was carried out to evaluate the economic burden of Parkinson's disease (PD) and factors independently associated with individual components of total cost in Singapore. METHODS: A consecutive sample of 195 patients with PD (mean age: 68.2, men: 51.8%) attending a tertiary neuroscience clinic were identified and interviewed using standardized questionnaires including a financial burden questionnaire, two Health Related Quality of Life (HRQoL) questionnaires and the Beck Depression Inventory questionnaire. RESULTS: Annual total cost of PD from a societal perspective was SGD11345 (USD10129) per patient, with direct cost accounted for 38.5% and indirect cost 61.5%. The main cost components for direct medical cost, direct non-medical cost, and indirect cost was pharmacotherapy (50.4%), home care (76.1%), and productivity loss (97.9%), respectively. In multiple linear regression analysis, higher education, younger age and longer duration of PD were associated with higher total cost. CONCLUSIONS: Parkinson's disease exerts a considerable burden on patients, health care system and society in Singapore. As productivity loss accounts for a large share of the economic burden imposed by PD, treatments and health care programmes with potential for returning patients to higher productivity are urgently needed.