Avinesh Pillai

Acetaminophen (Paracetamol) Improves Pain and Well-Being in People With Advanced Cancer Already Receiving a Strong Opioid Regimen: A Randomized, Double-Blind, Placebo-Controlled Cross-Over Trial

PURPOSE To determine whether adding regular acetaminophen (paracetamol) could improve pain and well-being in people with advanced cancer and pain despite strong opioids. PATIENTS AND METHODS Participants took acetaminophen for 48 hours and placebo for 48 hours. The order (acetaminophen or placebo first) was randomly allocated. Pain was the primary outcome. Preferences, number of opioid breakthrough doses, overall well-being, nausea and vomiting, drowsiness, constipation, and cold sweats were secondary outcomes. Patients rated themselves daily with visual analog scales (VAS) and a verbal numeric scale (VNS) for pain, all scaled from 0 to 10. RESULTS Thirty patients completed the trial. The oral opioid was morphine in 23 patients and hydromorphone in seven patients. The median daily opioid dose in oral morphine equivalents was 200 mg (range, 20 to 2,100 mg). Nonsteroidal anti-inflammatory drugs, corticosteroids, or both were used by 16 patients. Pain and overall well-being were better for patients receiving acetaminophen than for those receiving placebo. The mean difference was 0.4 (95% CI, 0.1 to 0.8; P =.03) in VNS for pain, 0.6 (95% CI, -0.1 to 1.3; P =.09) in VAS for pain, and 0.7 (95% CI, 0.0 to 1.4; P =.05) in VAS for overall well-being. More patients preferred the period they took acetaminophen (n = 14) than the period they took placebo (n = 8), but many had no preference (n = 8). There were no differences in the other outcomes. CONCLUSION Acetaminophen improved pain and well-being without major side effects in patients with cancer and persistent pain despite a strong opioid regimen. Its addition is worth considering in all such patients.

Glutamatergic Neurometabolites in Clozapine- Responsive and -Resistant Schizophrenia

Background: According to the current schizophrenia treatment guidelines, 3 levels of responsiveness to antipsychotic medication exist: those who respond to first-line antipsychotics, those with treatment-resistant schizophrenia who respond to clozapine, and those with clozapine-resistant or ultra-treatment resistant schizophrenia. Proton magnetic resonance spectroscopy studies indicate that antipsychotic medication decreases glutamate or total glutamate + glutamine in the brains of patients with schizophrenia and may represent a biomarker of treatment response; however, the 3 levels of treatment responsiveness have not been evaluated. Methods: Proton magnetic resonance spectroscopy spectra were acquired at 3 Tesla from patients taking a second generation non-clozapine antipsychotic (first-line responders), patients with treatment-resistant schizophrenia taking clozapine, patients with ultra-treatment resistant schizophrenia taking a combination of antipsychotics, and healthy comparison subjects. Results: Group differences in cerebrospinal fluid-corrected total glutamate + glutamine levels scaled to creatine were detected in the dorsolateral prefrontal cortex [df(3,48); F = 3.07, P = .04, partial η2 = 0.16] and the putamen [df(3,32); F = 2.93, P = .05, partial η2 = 0.22]. The first-line responder group had higher dorsolateral prefrontal cortex total glutamate + glutamine levels scaled to creatine than those with ultra-treatment resistant schizophrenia [mean difference = 0.25, standard error = 0.09, P = .04, family-wise error-corrected]. Those with treatment-resistant schizophrenia had higher total glutamate + glutamine levels scaled to creatine in the putamen than the first-line responders (mean difference = 0.31, standard error = 0.12, P = .05, family-wise error-corrected) and those with ultra-treatment-resistant schizophrenia (mean difference = 0.39, standard error = 0.12, P = .02, family-wise error-corrected). Conclusions: Total glutamate + glutamine levels scaled to creatine in the putamen may represent a marker of response to clozapine. Future studies should investigate glutamatergic anomalies prior to clozapine initiation and following successful treatment.

Recruiting equal numbers of indigenous and non-indigenous participants to a ‘polypill’ randomized trial

IntroductionMāori are disproportionately affected by cardiovascular disease (CVD), which is the main reason for the eight year difference in life expectancy between Māori and non-Māori. The primary care-based IMPACT (IMProving Adherence using Combination Therapy) trial evaluates whether fixed dose combination therapy (a “polypill”) improves adherence to guideline-based therapy compared with current care among people at high risk of CVD. Interventions shown in trials to be effective do not necessarily reduce ethnic disparities, and may in fact widen them. Indigenous populations with poorer health outcomes are often under-represented in trials so the effect of interventions cannot be assessed for them, specifically. Therefore, the IMPACT trial aimed to recruit as many Māori as non-Māori to assess the consistency of the effect of the polypill. This paper describes the methods and results of the recruitment strategy used to achieve this.MethodsExperienced Māori researchers were involved in trial governance throughout trial development and conduct. The trial Steering Committee included leading Māori researchers and was committed to equal recruitment of Māori and non-Māori. Additional funding and Māori research nurses were sought to allow home-based assessment, establishment of the relationship between research nurse and participant, more family involvement prior to enrollment, continuity of the research nurse-participant relationship, and acknowledgement of other Māori culturally important procedures, interactions, language and manners. Primary care practices with high enrollment of Māori were targeted, with over-sampling of potentially eligible Māori patients, lower thresholds for screening of Māori and 6 months continued Māori recruitment after non-Māori recruitment had finished.ResultsA total of 257 Māori and 256 non-Māori participants were randomized. Four Māori and eight non-Māori participants were randomized per research nurse per month. Potentially eligible Māori were more likely than non-Māori to proceed to subsequent stages of recruitment. Differences between randomized Māori and non-Māori were evident (e.g. Maori were less likely to have established coronary artery disease).ConclusionsRecruitment of equal numbers of indigenous and non-indigenous participants is possible if it is prioritised, adequately resourced and self-determination is supported.Trial registrationThe trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN12606000067572

Vitamin D status of Māori and non-Māori octogenarians in New Zealand: a cohort study (LiLACS NZ)

BACKGROUND AND OBJECTIVES This study assessed vitamin D status and its determinants in a cohort of octogenarians living within New Zealands Bay of Plenty and Lakes Districts. METHODS AND STUDY DESIGN Serum 25- hydroxyvitamin D [25(OH)D] concentration was measured in 209 Māori (aged 80-90 years) and 357 non-Māori (85 years), along with demographic, lifestyle, supplement use and other health data. RESULTS Mean [95% CI] 25(OH)D concentration was 69 [67 to 72] nmol/L, with 15% >100 nmol/L and 6 individuals >150 nmol/L. Concentrations in Māori (59 [55 to 62] 4 nmol/L) were lower than in non-Māori (75 [72 to 78] nmol/L; p<0.001), a difference maintained when adjusted for day-of-year measured. Vitamin D supplementation was reported by 98 participants (18%): including a greater proportion of women (24%) than men (11%; p<0.001) and of non-Māori (24%) than Māori (7%; p<0.001). Of those taking vitamin D, 49% took high oral doses (>=25 μg/day or equivalent) and five individuals took >50 μg/day. Vitamin D supplement use strongly and independently predicted seasonally- adjusted 25(OH)D concentration and was associated with 28 nmol/L higher levels than non-use. Other predictors included Māori ethnicity (10 nmol/L lower concentration than for non-Māori), and female gender (11 nmol/L lower). CONCLUSIONS Vitamin D status in New Zealand octogenarians appears higher than previously reported, particularly in non-Māori compared to Māori. Prescribed and non-prescribed oral vitamin D supplementation is prevalent in this group and a strong indicator of vitamin D status.

A brief treatment for fear of heights: A randomized controlled trial of a novel imaginal intervention

Objective To assess the effectiveness of a novel imaginal intervention for people with acrophobia. Methods The design was a randomized controlled trial with concealed randomization and blinded to other participants’ intervention. The intervention was a single novel imaginal intervention session or a 15-min meditation. The setting was in Auckland, New Zealand. The participants were a convenience sample of the public with a score >29 on the Heights Interpretation Questionnaire (HIQ), a questionnaire validated against actual height exposure. The primary outcomes were the proportion of participants with a score <26 on the HIQ at eight weeks and difference between the HIQ scores between the two arms of the study. Results Ninety-eight participants (92%) returned their questionnaire and were included in the intention to treat analysis. The HIQ score <26 was 34.6% (18/52) in the intervention group and 15.2% (7/46) in the control group RR = 2.26, 95% CI (1.05, 4.95) and p = 0.028. The numbers needed to treat is six 95% CI (3 to 36). Participants with scores <26 report their fear of heights is very much improved. There was a 4.5-point difference in the HIQ score at eight weeks (p = 0.055) on the multiple regression analysis. Conclusions This is the first randomized trial of this novel imaginal intervention which is probably effective, brief, easily learnt, and safe. It may be worth considering doing this prior to some of the longer or more expensive exposure therapies. This study will be of interest to family doctors, psychiatrists, and psychologists.

Inequity in timing of prenatal screening in New Zealand: Who are our most vulnerable?

In New Zealand (NZ), Maori and Pacific women are less likely to complete prenatal screening for Down syndrome and other aneuploidies than other ethnic groups. Young women <20 have low rates of completed screening compared with women >20 years. Women living in deprived areas have lower completed screen rates than women living in more affluent areas. Combined first trimester screening has a superior sensitivity (85%) compared with second trimester screening (75%) for trisomy 21. The relative contribution of demographic factors to timing of screening uptake (first vs second trimester) has not previously been examined.

Long-term exposure to neighborhood smoke from household heating and risk of respiratory and dermatological prescription medications - Growing Up in New Zealand child cohort study

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Supported Discharge Teams for older people in hospital acute care: a randomised controlled trial

Background Supported Discharge Teams aim to help with the transition from hospital to home, whilst reducing hospital length-of-stay. Despite their obvious attraction, the evidence remains mixed, ranging from strong support for disease-specific interventions to less favourable results for generic services. Objective To determine whether older people referred to a Supported Discharge Team have: (i) reduced length-of-stay in hospital; (ii) reduced risk of hospital readmission; and (iii) reduced healthcare costs. Methods Randomised controlled trial with follow-up to 6 months; 103 older women and 80 men (n = 183) (mean age 79), in hospital, were randomised to receive either Supported Discharge Team or usual care. Home-based rehabilitation was delivered by trained Health Care Assistants up to four times a day, 7 days a week, under the guidance of registered nurses, allied health and geriatricians for up to 6 weeks. Results Participants randomised to the Supported Discharge Team spent less time in hospital during the index admission (mean 15.7 days) in comparison to usual care (mean 21.6 days) (mean difference 5.9: 95% CI 0.6, 11.3 days: P = 0.03) and spent less time in hospital in the 6 months following discharge home. Supported discharge group costs were calculated at mean NZ

Increasing Incidence of Life-threatening Pertussis: A Retrospective Cohort Study in New Zealand

10,836 (SD NZ

Ethnic and Gender Differences in Preferred Activities among Māori and non-Māori of Advanced age in New Zealand

12,087) compared to NZ