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Fulltext Factors affecting patient compliance with anti-tuberculosis chemotherapy using the directly observed treatment, short-course strategy (DOTS)

O'Boyle SJ, Power JJ, Ibrahim MY, Watson JP

Int J Tuberc Lung Dis, 2002 Apr;6(4):307-12.
PMID: 11936739

SETTING: Kota Kinabalu and surrounding communities in Sabah, Malaysia.
OBJECTIVES: To establish factors affecting compliance of patients with anti-tuberculosis chemotherapy, their knowledge of the disease, and views on improving the DOTS strategy.
DESIGN: Interviews with compliant patients attending clinics for DOTS treatment and with non-compliant patients in their homes, in August and September 2000.
RESULTS: A total of 63 compliant and 23 non-compliant patients were interviewed. For non-compliant patients, reaching the treatment centre entailed greater cost (P < 0.005) and travel time (P < 0.005) compared to compliant patients. Cost of transport was the reason most frequently given for non-attendance. Non-compliant patients were more likely to have completed secondary education (P < 0.05), and to be working (P < 0.01). More non-compliant patients had family members who had had the disease (P < 0.01). There was no difference between the groups for overall tuberculosis knowledge scores; however, non-compliant patients were more likely to think that treatment could be stopped once they were symptom free (P < 0.01). Most patients (73%) felt that the DOTS system could be improved by provision of more information about tuberculosis.
CONCLUSION: Compliance with DOTS in the Kota Kinabalu area is affected by travel expenses, time spent travelling to treatment centres, and having family members who have had the disease. Patients would like more information on tuberculosis.
Study site: Tuberculosis clinics, Kota Kinabalu, Malaysia
Fulltext The lived experiences of chronic pain among immigrant Indian-Canadian women: A phenomenological analysis

Mustafa N, Einstein G, MacNeill M, Watt-Watson J

Can J Pain, 2020 Sep 24;4(3):40-50.
PMID: 33987510 DOI: 10.1080/24740527.2020.1768835

Background: Chronic pain is a growing public health concern affecting 1.5 million people in Canada. In particular, it is a concern among the expanding immigrant population, because immigrant groups report higher pain intensity than non-immigrants. In 2011, the Indian population became the largest visible minority group and continues to be the fastest growing. Though the prevalence of chronic pain among Canadian Indians is unknown, research has found a higher prevalence among Indian women than men in India, Malaysia, Singapore, and the United Kingdom, with women reporting more severe pain. An understanding of how pain is experienced by this particular group is therefore important for providing culturally sensitive care.
Aims: This study explores the lived experiences of chronic pain among immigrant Indian women in Canada.
Methods: Thirteen immigrant Indian women participated in one-on-one interviews exploring daily experiences of chronic pain.
Results: Using thematic analysis informed by van Manen's phenomenology of practice, four themes emerged: (1) the body in pain, (2) pain in the context of lived and felt space, (3) pain and relationships, and (4) pain and time. Women revealed that their experiences were shaped by gender roles and expectations enforced through culture. Specifically, a dual gender role was identified after immigration, in which women had to balance traditional household responsibilities of family labor and care alongside employment outside the home, exacerbating pain.
Conclusions: This research uncovers the multifaceted nature of chronic pain and identifies factors within the sociocultural context that may place particular groups of women at greater risk of living with pain.
Fulltext A balanced randomised placebo controlled blinded phase IIa multi-centre study to investigate the efficacy and safety of AUT00063 versus placebo in subjective tinnitus: The QUIET-1 trial

Hall DA, Ray J, Watson J, Sharman A, Hutchison J, Harris P, et al.

Hear Res, 2019 06;377:153-166.
PMID: 30939361 DOI: 10.1016/j.heares.2019.03.018

AUT00063 is an experimental new medicine that has been demonstrated to suppress spontaneous hyperactivity by modulating the action of voltage-gated potassium-channels in central auditory cortical neurons of a rodent model. This neurobiological property makes it a good candidate for treating the central component of subjective tinnitus but this has not yet been tested in humans. The main purpose of the QUIET-1 (QUest In Eliminating Tinnitus) trial was to examine the effect of AUT00063 on the severity of tinnitus symptoms in people with subjective tinnitus. The trial was a randomised, placebo-controlled, observer, physician and participant blinded multi-centre superiority trial with two parallel groups and a primary endpoint of functional impact on tinnitus 28 days after the first drug dosing day. The trial design overcame the scale and logistical challenges of delivering a scientifically robust, statistically powered multi-centre study for subjective tinnitus within the National Health Service in England. The trial was terminated early for futility. Overall, 212 participants consented across 18 sites with 91 participants randomised to groups using age, gender, tinnitus symptom severity and hearing status as minimisation factors. While the pharmacokinetic markers confirm the uptake of AUT00063 in the body, within the expected therapeutic range, with respect to clinical benefit findings indicated that AUT00063 was not effective in alleviating tinnitus symptoms (1.56 point change in Tinnitus Functional Index). In terms of clinical harms, results indicated that a daily dose of 800 mg capsules of AUT00063 taken for 28 days was safe and well tolerated. These findings provide significant advances in the drug development field for hearing sciences, but raise questions about the predictive validity of certain rodent models of noise-induced hearing loss and tinnitus, as least for the mechanism evaluated in the present study. Trial Registration: (EudraCT) 2014-002179-27; NCT02315508.
Fulltext A molecular barcode to inform the geographical origin and transmission dynamics of Plasmodium vivax malaria

Diez Benavente E, Campos M, Phelan J, Nolder D, Dombrowski JG, Marinho CRF, et al.

PLoS Genet, 2020 02;16(2):e1008576.
PMID: 32053607 DOI: 10.1371/journal.pgen.1008576

Although Plasmodium vivax parasites are the predominant cause of malaria outside of sub-Saharan Africa, they not always prioritised by elimination programmes. P. vivax is resilient and poses challenges through its ability to re-emerge from dormancy in the human liver. With observed growing drug-resistance and the increasing reports of life-threatening infections, new tools to inform elimination efforts are needed. In order to halt transmission, we need to better understand the dynamics of transmission, the movement of parasites, and the reservoirs of infection in order to design targeted interventions. The use of molecular genetics and epidemiology for tracking and studying malaria parasite populations has been applied successfully in P. falciparum species and here we sought to develop a molecular genetic tool for P. vivax. By assembling the largest set of P. vivax whole genome sequences (n = 433) spanning 17 countries, and applying a machine learning approach, we created a 71 SNP barcode with high predictive ability to identify geographic origin (91.4%). Further, due to the inclusion of markers for within population variability, the barcode may also distinguish local transmission networks. By using P. vivax data from a low-transmission setting in Malaysia, we demonstrate the potential ability to infer outbreak events. By characterising the barcoding SNP genotypes in P. vivax DNA sourced from UK travellers (n = 132) to ten malaria endemic countries predominantly not used in the barcode construction, we correctly predicted the geographic region of infection origin. Overall, the 71 SNP barcode outperforms previously published genotyping methods and when rolled-out within new portable platforms, is likely to be an invaluable tool for informing targeted interventions towards elimination of this resilient human malaria.
Fulltext The haematological consequences of Plasmodium vivax malaria after chloroquine treatment with and without primaquine: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis

Commons RJ, Simpson JA, Thriemer K, Chu CS, Douglas NM, Abreha T, et al.

BMC Med, 2019 08 01;17(1):151.
PMID: 31366382 DOI: 10.1186/s12916-019-1386-6

BACKGROUND: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax.
METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model.
RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p 25% to 5 g/dL.
CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals.
TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.