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A retrospective serological suvey of Royal Marines previously exposed to Pseudomonas pseudomallei in South East Asia

Preston PJ, Lightfoot N, Clarke P

Trans R Soc Trop Med Hyg, 1976;70(4):335-7.
PMID: 1006764

Following the suggestion that it was possible that cases of melioidosis amongst those who had been exposed abroad in the past, might be escaping notice, 487 Royal Marines were examined by indirect haemagglutination studies. Four hundred and eleven of these subjects had served for variable times in areas where melioidosis has been known to occur in Indonesia and Malaya, between 1960 and 1974, occupied in activities in the jungle and paddy fields during which exposure to the disease was to be expected. No evidence of residual subclinical melioidosis was found and it seems unlikely that recrudescent disease will prove to be a problem in the future for English servicemen who have been in South East Asia.
Immediate selective laryngeal reinnervation in vagal paraganglioma patients

Mat Baki M, Clarke P, Birchall MA

J Laryngol Otol, 2018 Sep;132(9):846-851.
PMID: 30180919 DOI: 10.1017/S0022215118000476

OBJECTIVE: This prospective case series aimed to present the outcomes of immediate selective laryngeal reinnervation.
METHODS: Two middle-aged women with vagal paraganglioma undergoing an excision operation underwent immediate selective laryngeal reinnervation using the phrenic nerve and ansa cervicalis as the donor nerve. Multidimensional outcome measures were employed pre-operatively, and at 1, 6 and 12 months post-operatively.
RESULTS: The voice handicap index-10 score improved from 23 (patient 1) and 18 (patient 2) at 1 month post-operation, to 5 (patient 1) and 1 (patient 2) at 12 months. The Eating Assessment Tool 10 score improved from 20 (patient 1) and 24 (patient 2) at 1 month post-operation, to 3 (patient 1) and 1 (patient 2) at 12 months. There was slight vocal fold abduction observed in patient one and no obvious abduction in patient two.
CONCLUSION: Selective reinnervation is safe to perform following vagal paraganglioma excision conducted on the same side. Voice and swallowing improvements were demonstrated, but no significant vocal fold abduction was achieved.
Fulltext Cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy

Saad N, Alberio R, Johnson AD, Emes RD, Giles TC, Clarke P, et al.

Oncotarget, 2018 Mar 23;9(22):16008-16027.
PMID: 29662623 DOI: 10.18632/oncotarget.24664

Inducing stable control of tumour growth by tumour reversion is an alternative approach to cancer treatment when eradication of the disease cannot be achieved. The process requires re-establishment of normal control mechanisms that are lost in cancer cells so that abnormal proliferation can be halted. Embryonic environments can reset cellular programmes and we previously showed that axolotl oocyte extracts can reprogram breast cancer cells and reverse their tumorigenicity. In this study, we analysed the gene expression profiles of oocyte extract-treated tumour xenografts to show that tumour reprogramming involves cell cycle arrest and acquisition of a quiescent state. Tumour dormancy is associated with increased P27 expression, restoration of RB function and downregulation of mitogen-activated signalling pathways. We also show that the quiescent state is associated with increased levels of H4K20me3 and decreased H4K20me1, an epigenetic profile leading to chromatin compaction. The epigenetic reprogramming induced by oocyte extracts is required for RB hypophosphorylation and induction of P27 expression, both occurring during exposure to the extracts and stably maintained in reprogrammed tumour xenografts. Therefore, this study demonstrates the value of oocyte molecules for inducing tumour reversion and for the development of new chemoquiescence-based therapies.
Functional Outcomes Following Delayed Laryngeal Reinnervation Of Patients with Vagal Paralysis After Paraganglioma and Schwannoma Surgery

Candelo E, Borsetto D, Obholzer R, Clarke P, MatBaki M, Birchall M

J Voice, 2023 Jul;37(4):610-615.
PMID: 33994255 DOI: 10.1016/j.jvoice.2021.03.021

PURPOSE: We present a prospective case series that aimed to report the functional (voice and swallowing) outcomes of delayed laryngeal reinnervation following vagal interruption by resection of vagal paraganglioma and schwannoma.
MATERIALS AND METHODS: A dedicated, anonymized database was established in 2012 with a minimum eighteen-month follow up set for this report. Internationally validated self- and observer-reported measures were recorded preoperatively and at six, 12 and, 18 months together with demographics, diagnoses, and operative details.
RESULTS: A total of eight patients with a median age of 46 (37-54) underwent excision of vagal paraganglioma (five) and schwannoma (three) with few mild complications. Three underwent selective and five non selective reinnervation. Seven out of eight patients underwent synchronous injection medialization. The voice handicap index (VHI-30) improved from a baseline median 83 (range 52-102) to 7.5 (5-58) at 18 months; maximum phonation time improved from median 8 (range 5-15) to 10.5 (8.5-11); voice grade ("G" in grade, roughness, breathiness, asthenia, and strain [GRBAS] scoring) improved from median three (severe impairment, range 0-3) to one (mild impairment, 0-2); Eating Assessment Tool (EAT-10) score improved from median 12 (range 3.5-27) preoperatively to one (0-16); and reflux symptom index (RSI) improved from median 25 (range 17-36) to 7 (0-36). One patient exhibited no discernible reinnervation, while the remainder exhibited good cord bulk and tone, though without purposive abduction.
CONCLUSION: Delayed laryngeal reinnervation for high vagal paralysis is a safe technique associated with good voice and swallowing outcomes by 12-18 months. Potential confounders in this small series and the absence of a control arm both limit conclusions, but this study suggests that further prospective, controlled studies, and/or case registration are merited.
Fulltext Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management

Gao N, Dakin HA, Holman RR, Lim LL, Leal J, Clarke P

Pharmacoeconomics, 2024 Sep;42(9):1017-1028.
PMID: 38922488 DOI: 10.1007/s40273-024-01398-4

OBJECTIVES: Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates.
AIMS: (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations.
METHODS: Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations.
RESULTS: All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations.
DISCUSSION: Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients' health, expenditure and quality of life.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01144338 and NCT00790205.
Fulltext Health poverty among people with type 2 diabetes mellitus (T2DM) in Malaysia

Parra-Mujica F, Roope LS, Abdul-Aziz A, Mustapha F, Ng CW, Rampal S, et al.

Soc Sci Med, 2024 Jan;340:116426.
PMID: 38016309 DOI: 10.1016/j.socscimed.2023.116426

In the context of the escalating burden of diabetes in low and middle-income countries (LMICs), there is a pressing concern about the widening disparities in care and outcomes across socioeconomic groups. This paper estimates health poverty measures among individuals with type 2 diabetes mellitus (T2DM) in Malaysia. Using data from the National Diabetes Registry between 2009 and 2018, the study linked 932,855 people with T2DM aged 40-75 to death records. Cox proportional hazards models were used to estimate the 5-year survival probabilities for each patient, stratified by age and sex, while controlling for comorbidities and area-based indicators of socio-economic status (SES), such as district-level asset-based indices and night-time luminosity. Measures of health poverty, based on the Foster-Greer-Thorbecke (FGT) measures, were employed to capture excessive risk of premature mortality. Two poverty line thresholds were used, namely a 5% and 10% reduction in survival probability compared to age and sex-adjusted survival probability of the general population. Counterfactual simulations estimated the extent to which comorbidities contribute to health poverty. 43.5% of the sample experienced health poverty using the 5% threshold, and 8.9% were health poor using the 10% threshold. Comorbidities contribute 2.9% for males and 5.4% for females, at the 5% threshold. At the 10% threshold, they contribute 7.4% for males and 3.4% for females. If all patients lived in areas of highest night-light intensity, poverty would fall by 5.8% for males and 4.6% for females at the 5% threshold, and 4.1% for males and 0.8% for females at the 10% threshold. In Malaysia, there is a high incidence of health poverty among people with diabetes, and it is strongly associated with comorbidities and area-based measures of SES. Expanding the application of health poverty measurement, through a combination of clinical registries and open spatial data, can facilitate simulations for health poverty alleviation.
Fulltext Aspects of Multicomponent Integrated Care Promote Sustained Improvement in Surrogate Clinical Outcomes: A Systematic Review and Meta-analysis

Lim LL, Lau ESH, Kong APS, Davies MJ, Levitt NS, Eliasson B, et al.

Diabetes Care, 2018 06;41(6):1312-1320.
PMID: 29784698 DOI: 10.2337/dc17-2010

OBJECTIVE: The implementation of the Chronic Care Model (CCM) improves health care quality. We examined the sustained effectiveness of multicomponent integrated care in type 2 diabetes.

RESEARCH DESIGN AND METHODS: We searched PubMed and Ovid MEDLINE (January 2000-August 2016) and identified randomized controlled trials comprising two or more quality improvement strategies from two or more domains (health system, health care providers, or patients) lasting ≥12 months with one or more clinical outcomes. Two reviewers extracted data and appraised the reporting quality.

RESULTS: In a meta-analysis of 181 trials (N = 135,112), random-effects modeling revealed pooled mean differences in HbA1c of -0.28% (95% CI -0.35 to -0.21) (-3.1 mmol/mol [-3.9 to -2.3]), in systolic blood pressure (SBP) of -2.3 mmHg (-3.1 to -1.4), in diastolic blood pressure (DBP) of -1.1 mmHg (-1.5 to -0.6), and in LDL cholesterol (LDL-C) of -0.14 mmol/L (-0.21 to -0.07), with greater effects in patients with LDL-C ≥3.4 mmol/L (-0.31 vs. -0.10 mmol/L for <3.4 mmol/L; Pdifference = 0.013), studies from Asia (HbA1c -0.51% vs. -0.23% for North America [-5.5 vs. -2.5 mmol/mol]; Pdifference = 0.046), and studies lasting >12 months (SBP -3.4 vs. -1.4 mmHg, Pdifference = 0.034; DBP -1.7 vs. -0.7 mmHg, Pdifference = 0.047; LDL-C -0.21 vs. -0.07 mmol/L for 12-month studies, Pdifference = 0.049). Patients with median age <60 years had greater HbA1c reduction (-0.35% vs. -0.18% for ≥60 years [-3.8 vs. -2.0 mmol/mol]; Pdifference = 0.029). Team change, patient education/self-management, and improved patient-provider communication had the largest effect sizes (0.28-0.36% [3.0-3.9 mmol/mol]).

CONCLUSIONS: Despite the small effect size of multicomponent integrated care (in part attenuated by good background care), team-based care with better information flow may improve patient-provider communication and self-management in patients who are young, with suboptimal control, and in low-resource settings.