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Abstract The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

Abstract Objectives To determine whether exempting people (with high health needs and living in areas of high deprivation) from a $5 prescription charge reduces hospital use. Design Two-group parallel prospective randomised controlled trial. Setting People living in the community in various regions of New Zealand. Participants One thousand sixty one people who lived in areas of high socioeconomic deprivation, and either took medicines for diabetes, took antipsychotic medicines, or had chronic obstructive pulmonary disease (COPD). Of the 1053 who completed the study, just under half (49%) were Māori. Interventions Participants were individually randomized (1–1 ratio) to either be exempted from the standard $5 charge per prescription item for one year (2020-2021) (n = 591) or usual care (n = 469). Those in the intervention group did not pay the standard NZ$5 charge, and pharmacies billed the study for these. Participants continued to pay any other costs for prescription medicines. Those in the control group continued to pay all prescription charges for the year although they may have received one-off assistance from other agencies. Main outcome measures The primary outcome was length of stay (hospital bed-days). Secondary outcomes presented in this paper included: all-cause hospitalisations, hospitalisations for diabetes/mental health problems/COPD, deaths, and emergency department visits. Results The trial was under-powered because the recruitment target was not met. There was no statistically significant reduction in the primary outcome, hospital bed-days (IRR = 0.68, CI: 0.54 to 1.05). Participants in the intervention group were significantly less likely to be hospitalised during the study year than those in the control group (OR = 0.70, CI: 0.54 to 0.90). There were statistically significant reductions in the number of hospital admissions for mental health problems (IRR = 0.39, CI: 0.17 to 0.92), the number of admissions for COPD (IRR = 0.37, CI: 0.16 to 0.85), and length of stay for COPD (IRR 0.20, CI: 0.07 to 0.60). Apart from all-cause mortality and diabetes length of stay, all measures were better for the intervention group than the control group. Conclusions Eliminating a small co-payment appears to have had a substantial effect on patients’ risk of being hospitalised. Given the small amount of revenue gathered from the charges, and the comparative large costs of hospitalisations, the results suggest that these charges are likely to increase the overall cost of healthcare, as well as exacerbate ethnic inequalities. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12618001486213 registered on 04/09/2018.

We designed pyrochlore-type potassium niobate (KN) and potassium tantalate (KT) by introducing silver ions to improve their antibacterial efficiency. KN and KT samples were used as ion-exchangeable parent compounds, and molten AgNO3 was used for the ion-exchange reaction. The formation of silver ion-exchanged compounds with various molar ratios, which was investigated by X-ray diffraction (XRD), indicated a clear structural transformation of KN after complete ion-exchange. The antibacterial efficacy of these samples was investigated using the colony count method, and the relative antibacterial activity was compared based on the area of the inhibition zone. The results indicated that silver ion-exchanged samples with molar ratios of Ag/Nb = 0.05, 0.44, 0.67, and Ag/Ta = 0.07, 0.44 0.64 exhibited complete (100%) antibacterial activity against Staphylococcus aureus (gram-positive) and Escherichia coli (gram-negative). Among the silver ion-exchanged samples, KAN1 and KAT1 exhibited the highest antibacterial activities because of the controlled release of Ag+ ions through their tunnel structure. In this study, it was found that tunable silver-release properties of pyrochlore-type niobate and tantalate enable the optimization of discharged Ag+ ions, which inhibits the bacterial efficacy in different extents, thus suggesting their use in various biomedical applications.

Abstract Background Research examining psychological distress in people who have experienced an injury has focused on those with serious injuries or specific injury types, and has not involved long-term follow up. The aims of this investigation were to describe the prevalence of, and factors contributing to, psychological distress in a cohort of people with a broad range of injuries. Methods The Prospective Outcomes of Injury Study (POIS) is a longitudinal cohort study of 2856 injured New Zealanders recruited from a national insurance entitlement claims register between 2007 and 2009. Participants were interviewed approximately 3, 12, and 24 months after their injury. The Kessler Psychological Distress Scale (K6) was used to measure psychological distress at each interview. Results 25% of participants reported clinically relevant distress (K6 ≥ 8) 3 months post-injury, 15% reported distress at 12 months, and 16% reported distress at 24 months. Being 45 years or older, Māori or Pacific ethnicity, experiencing pre-injury mental health conditions, having inadequate pre-injury income, reporting poor pre-injury health or trouble accessing healthcare, having a severe injury or an injury resulting from assault, and reporting clinically relevant distress 3 months post-injury were independently associated with an increased risk of distress 12 months post-injury. The majority of these associations were also evident with respect to distress 24 months post-injury. Conclusions Distress is common after injury among people with a broad range of injury types and severities. Screening for distress early after injury is important to identify individuals in need of targeted support.

Objective To identify factors associated with better or poorer self-reported health status in New Zealand military Veterans.Design A cross-sectional survey.Participants The participants of interest were the 3874 currently serving Veterans who had been deployed to a conflict zone, but all Veterans were eligible to participate.Study variables The EQ-5D-5L, asking about problems across five dimensions (mobility, self-care, usual activities, pain or discomfort and anxiety or depression), with five levels of severity (eg, no, slight, moderate, severe or extreme problems), also containing a Visual Analogue Scale (EQ-VAS) to self-assess health state, scaled from 0 (worst) to 100 (best) imagined health.Hypothetical relationships with better health were positive social support, sleep and psychological flexibility; with poorer health, post-traumatic stress, exposure to psychological trauma, distress and hazardous drinking.Results The EQ5-D-5L was completed by 1767 Veterans, 1009 serving, a response rate of 26% from that group, 1767 completing the EQ5-D, 1458 who had deployed, 288 who had not and the 21 who did not provide deployment data. Of these, 247 were not used in the analysis due to missing values in one or more variables, leaving 1520 for analysis.A significantly higher proportion of Veterans reported ‘any problems’ rather than ‘no problems’ with four EQ-5D dimensions: mobility, self-care, usual activities and pain or discomfort, but no difference in anxiety or depression. Age, length of service, deployment, psychological flexibility and better sleep quality were associated with higher EQ-VAS scores; distress with lower EQ-VAS scores.Conclusion In this sample of New Zealand Veterans, psychological flexibility and good sleep are associated with better self-rated health, and distress and poor sleep with diminished health. These factors might be used as sentinel health indicators in assessing Veteran health status, and cognitive–behavioural therapy encompassing these domains may be useful in improving the health of New Zealand Veterans.

Objectives To determine the epidemiology of healthcare harm observable in general practice records.Design Retrospective cohort records review study.Setting 72 general practice clinics were randomly selected from all 988 New Zealand clinics stratified by rurality and size; 44 clinics consented to participate.Participants 9076 patient records were randomly selected from participating clinics.Intervention Eight general practitioners examined patient records (2011–2013) to identify harms, harm severity and preventability. Analyses were weighted to account for the stratified sampling design and generalise findings to all New Zealand patients.Main outcome measures Healthcare harm, severity and preventability.Results Reviewers identified 2972 harms affecting 1505 patients aged 0–102 years. Most patients (82.0%, weighted) experienced no harm. The estimated incidence of harm was 123 per 1000 patient-years. Most harms (2160; 72.7%, 72.4% weighted) were minor, 661 (22.2%, 22.8% weighted) were moderate, and 135 (4.5%, 4.4% weighted) severe. Eleven patients died, five following a preventable harm. Of the non-fatal harms, 2411 (81.6%, 79.4% weighted) were considered not preventable. Increasing age and number of consultations were associated with increased odds of harm. Compared with patients aged ≤49 years, patients aged 50–69 had an OR of 1.77 (95% CI 1.61 to 1.94), ≥70 years OR 3.23 (95% CI 2.37 to 4.41). Compared with patients with ≤3 consultations, patients with 4–12 consultations had an OR of 7.14 (95% CI 5.21 to 9.79); ≥13 consultations OR 30.06 (95% CI 21.70 to 41.63).Conclusions Strategic balancing of healthcare risks and benefits may improve patient safety but will not necessarily eliminate harms, which often arise from standard care. Reducing harms considered ‘not preventable’ remains a laudable challenge.

Introduction Prescription charges prevent many people from accessing the medicines they need to maintain or improve their health. In New Zealand, where most people pay $5 per prescription item, Māori and Pacific peoples, those living in most deprived areas and those with chronic health conditions are the most likely to report that cost prevents them from accessing medicines.Methods and analysis This randomised controlled trial (RCT) will evaluate the effect of removing prescription charges on health outcomes and healthcare utilisation patterns of people with low income and high health needs. We will enrol 2000 participants: half will be allocated to the intervention group and we will pay for their prescription charges for 12 months. The other half will receive usual care. The primary outcome will be hospital bed-days. Secondary outcomes will be: all-cause and diabetes/mental health-specific hospitalisations, prescription medicines dispensed (number and type), deaths, emergency department visits and quality of life as measured by the 5-level EQ-5D version. Costs associated with these outcomes will be compared in an economic substudy. A qualitative substudy will also help understand the impact of free prescriptions on participant well-being using in-depth interviews.Discussion Being unable to afford prescription medicines is only one of many factors that influence adherence to medicines, but removing prescription charges is relatively simple and in New Zealand would be cheap compared with other policy changes. This RCT will help identify the extent of the impact of a simple intervention to improve access to medicines on health outcomes and health service utilisation.Ethics and dissemination This study was approved by the Central Health and Disability Ethics Committee (NZ) in July 2019 (19/CEN/33). Findings will be reported in peer-reviewed publications, as well as in professional newsletters, mainstream media and through public meetings.Trial registration number ACTRN12618001486213p.

Summary: Although the intrinsic mechanisms that control whether stem cells divide symmetrically or asymmetrically underlie tissue growth and homeostasis, they remain poorly defined. We report that the RNA-binding protein fragile X mental retardation protein (FMRP) limits the symmetric division, and resulting expansion, of the stem cell population during adaptive intestinal growth in Drosophila. The elevated insulin sensitivity that FMRP-deficient progenitor cells display contributes to their accelerated expansion, which is suppressed by the depletion of insulin-signaling components. This FMRP activity is mediated solely via a second conserved RNA-binding protein, LIN-28, known to boost insulin signaling in stem cells. Via LIN-28, FMRP controls progenitor cell behavior by post-transcriptionally repressing the level of insulin receptor (InR). This study identifies the stem cell-based mechanism by which FMRP controls tissue adaptation, and it raises the possibility that defective adaptive growth underlies the accelerated growth, gastrointestinal, and other symptoms that affect fragile X syndrome patients. : Luhur et al. report that FMRP acts via LIN-28 in progenitor cells to dampen the adaptive expansion of intestinal tissue in the fruit fly, raising the possibility that defective LIN28-mediated adaptive growth underlies some of the symptoms that affect fragile X syndrome patients. Keywords: FMRP, fmr1, LIN-28, insulin receptor, IIS, adaptive growth, tissue resizing, intestinal stem cell, insulin sensitivity

Background: Faculty of Medicine, University of Kelaniya, Sri Lanka conducts a one month under graduate training programme during their fourth year at the University family practice centre. Students get training in history taking, clinical examination, patient management and practice management during this attachment. This study was conducted to look at the patients′ attitude towards student participation during consultation. Materials and Methods: This was a descriptive cross sectional study. All the patients who were 16 years and above during a 2 month period were included in the study. Structured questionnaire was administered by demonstrators following a consultation where students were present. Their demographic data, number of consultations with student participation and questions related to presence of students at various stages of the consultation were asked. Results: Total of 85 patients took part in the study and 81.3% of them were females. 88.8% were of the opinion that they benefited by the interaction with medical students while 93.8% thought students understood their problems. 26.3% patients preferred a medical student of the same sex during consultation while 71.3 had not expressed any opinion in this regard. Only 3.8% and 5% wanted the doctor alone during history taking and examination respectively. Almost every patient was happy that they could help the undergraduate training. Discussion: As expected results of the study showed that patients were willing to take part in undergraduate training without any reservation. These results are compatible with the previous studies done in the western world and data is not available form either Sri Lanka or other Asian countries.