Open access

The OBS UK Dashboard: an interactive tool for representative trial site selection to facilitate equality and diversity in maternity research (2024)

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Type of publication:

Journal article

Author(s):

*Elsmore, Amy; Rai, Tanvi; Pallmann, Philip; Townson, Julia; Kotecha, Sarah; Black, Mairead; Sanders, Julia; Collis, Rachel; Collins, Peter; Karunakaran, Bala; Wu, Pensee; Bell, Sarah; *Parry-Smith, William

Citation:

Trials. 25(1):629, 2024 Sep 27.

Abstract:

BACKGROUND: Obstetric Bleeding Study UK (OBS UK) (award ID: 152057) is a National Institute for Health and Care Research (NIHR)-funded stepped wedge cluster randomised controlled trial of a complex intervention for postpartum haemorrhage. This was developed in Wales and evaluated in a feasibility study, with improvements in maternal outcomes observed. Generalisability of the findings is limited by lack of control data and limited ethnic diversity in the Welsh obstetric patient population compared to the United Kingdom (UK): 94% of the Welsh population identifies as White, versus 82% in the UK. Non-White ethnicity and socioeconomic deprivation are linked to increased risk of adverse maternal outcomes. traditionally, decisions regarding site selection are based on desire to complete trials on target in 'tried and tested' research active institutions. To ensure widespread applicability of the results and investigate the impact of ethnicity and social deprivation on trial outcomes, maternity units were recruited that represent the ethnic diversity and social deprivation profiles of the UK. METHOD: Using routinely collected, publicly available data, an interactive dashboard was developed that demonstrates the demographics of the population served by each maternity unit in the UK, to inform site recruitment. Data on births per year, ethnic and socioeconomic group of the population for each maternity unit, across the UK, were integrated into the dashboard. RESULTS: The dashboard demonstrates that OBS UK trial sites reflect the ethnic and socioeconomic diversity of the UK (study vs UK population ethnicity: White 79.2% vs 81.7%, Asian 10.5% vs 9.3%, Black 4.7% vs 4.0%, Mixed 2.5% vs 2.9%, Other 3.0% vs 2.1%) with variation in site demography, size and location. Missing data varied across sites and nations and is presented. CONCLUSION: The NIHR equality, diversity and inclusion strategy states studies must widen

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Interpretable Machine Learning for Predicting Multiple Sclerosis Conversion from Clinically Isolated Syndrome (2024)

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Type of publication:
Journal article

Author(s):
Daniel E.C.; Tirunagari S.; Batth K.; Windridge D.; *Balla Y.

Citation:
medRxiv. (no pagination), 2024. Date of Publication: 19 Jul 2024. [preprint]

Abstract:
Background: Machine learning (ML) prediction of clinically isolated syndrome (CIS) conversion to multiple sclerosis (MS) could be used as a remote, preliminary tool by clinicians to identify high-risk patients that would benefit from early treatment. Objective(s): This study evaluates ML models to predict CIS to MS conversion and identifies key predictors. Method(s): Five supervised learning techniques (Naive Bayes, Logistic Regression, Decision Trees, Random Forests and Support Vector Machines) were applied to clinical data from 138 Lithuanian and 273 Mexican CIS patients. Seven different feature combinations were evaluated to determine the most effective models and predictors. Result(s): Key predictors common to both datasets included sex, presence of oligoclonal bands in CSF, MRI spinal lesions, abnormal visual evoked potentials and brainstem auditory evoked potentials. The Lithuanian dataset confirmed predictors identified by previous clinical research, while the Mexican dataset partially validated them. The highest F1 score of 1.0 was achieved using Random Forests on all features for the Mexican dataset and Logistic Regression with SMOTE Upsampling on all features for the Lithuanian dataset. Conclusion(s): Applying the identified high-performing ML models to the CIS patient datasets shows potential in assisting clinicians to identify high-risk patients.

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Clinical decision support systems for maternity care: a systematic review and meta-analysis. (2024)

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Type of publication:
Journal article

Author(s):
Cockburn N.; Osborne C.; Withana S.; *Elsmore A.; *Nanjappa R.; South M.; *Parry-Smith W.; Taylor B.; Chandan J.S.; Nirantharakumar K.

Citation:
eClinicalMedicine. 76 (no pagination), 2024. Article Number: 102822. Date of Publication: October 2024.

Abstract:
Background: The use of Clinical Decision Support Systems (CDSS) is increasing throughout healthcare and may be able to improve safety and outcomes in maternity care, but maternity care has key differences to other disciplines that complicate the use of CDSS. We aimed to identify evaluated CDSS and synthesise evidence of their impact on maternity care. Method(s): We conducted a systematic review for articles published before 24th May 2024 that described i) CDSS that ii) investigated the impact of their use iii) in maternity settings. Medline, CINAHL, CENTRAL and HMIC were searched for articles relating to evaluations of CDSS in maternity settings, with forward- and backward-citation tracing conducted for included articles. Risk of bias was assessed using the Mixed Methods Assessment Tool, and CDSS were described according to the clinical problem, purpose, design, and technical environment. Quantitative results from articles reporting appropriate data were meta-analysed to estimate odds of a CDSS achieving its desired outcome using a multi-level random effects model, first by individual CDSS and then across all CDSS. PROSPERO ID: CRD42022348157. Finding(s): We screened 12,039 papers and included 87 articles describing 47 unique CDSS. 24 articles (28%) described randomised controlled trials, 30 (34%) described non-randomised interventional studies, 10 (11%) described mixed methods studies, 10 (11%) described qualitative studies, 7 (8%) described quantitative descriptive studies, and 7 (8%) described economic evaluations. 49 (56%) were in High-Income Countries and 38 (44%) in Low- and Middle-Income countries, with no CDSS trialled in both income categories. Meta-analysis of 35 included studies found an odds ratio for improved outcomes of 1.69 (95% confidence interval 1.24-2.30). There was substantial variation in effects, aims, CDSS types, context, study designs, and outcomes. Interpretation(s): Most CDSS evaluations showed improvements in outcomes, but there was heterogeneity in all aspects of design and evaluation of systems. CDSS are increasingly important in delivering healthcare, and Electronic Health Records and mHealth will increase their availability, but traditional epidemiological methods may be limited in guiding design and demonstrating effectiveness due to rapid CDSS development lifecycles and the complex systems in which they are embedded. Development methods that are attentive to context, such as Human Centred Design, will help to meet this need.

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To study morbidity and mortality related to ileostomy/colostomy closure at tertiary care hospital (2024)

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Type of publication:
Journal article

Author(s):
Gilani S.S.; *Shahzeb M.; Salman D.M.; Nadeem M.; Khan S.; Thomas J.J.; Almesri A.

Citation:
Journal of Population Therapeutics and Clinical Pharmacology. 31(8) (pp 853-858), 2024. Date of Publication: 01 Aug 2024.

Abstract:
Background and Aim: Gastrointestinal stomas main function is to divert the flow away from a difficult anastomoses or intestinal obstruction. There is now a trend toward avoiding permanent stomas, and temporary loop stomas often used to protect anastomotic or distal bowel segments in high-risk patients. The present study aimed to determine the morbidity-mortality after ileostomy or colostomy closure. Patients and Methods: This comparative observational study investigated 42 cases of ileostomy and colostomy closure in the Surgical Unit of Jinnah Hospital, Lahore from January 2020 to January 2024. Patients were divided into two groups; Group-I (Ileostomy closure) and Group-II (Colostomy closure). Demographic details such as age and gender, Clinical details such as indications, types of stoma technique used, and operative times, length of hospital stay, morbidity, and mortality recorded. SPSS version 26 was used for data analysis. Result(s): The overall mean age was 46.8+/-6.52 years (15-75 years). Out of 42 cases, 28 (66.7%) underwent ileostomy and 14 (33.3%) underwent colostomy closure. The most prevalent indication for closure was protection of anastomosis in both stoma groups. The interval between creation and closure of stoma was shorter (117.8 days) in Group-I than Group-II (162.4 days). The incidence of hand sewing sutures and stapled technique was 32 (76.2%) and 10 (23.8%), respectively. The Group-II patients took 107.9+/-5.24 minutes as operative time which was significantly higher than 82.96+/-8.84 minutes in Group-I. The prevalence of morbidity in Group-I and Group-II was 10.7% (n=3) and 14.3% (n=2), respectively. Prolong hospital stay was required in Group-II. No mortality case reported in both stoma groups. Conclusion(s): The present study observed that Stomatal closure well tolerated procedure, with low morbidity and mortality. The results suggest that ileostomy closure is a relatively simple procedure.

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Parenteral Therapy in Domiciliary and Outpatient Setting: A Critical Review of the Literature (2023)

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Type of publication:
Journal article

Author(s):
*Puzovic M.; Morrissey H.; Ball P.A.

Citation:
Archives of Pharmacy Practice. 14(2) (pp 1-12), 2023. Date of Publication: 2023.

Abstract:
The clinical homecare sector is often associated with high-cost drug parenteral (injectable) therapy treatments and has been rapidly growing in the United Kingdom (UK) at a 20% annual rate. It was estimated that this could further rise to 60% if extended to all medicines that are considered to be suitable for care at home. The latest data shows that the homecare medicines services sector continues to grow in number and complexity, with over 500,000 patients and a spend of UK3.2 billion in 2021. Given the extent of the National Health Service (NHS) expenditure and the number of patients involved, it is essential to understand and explore the patients' and HCPs' experiences, views, and perceptions of this therapy. As identified during this literature review, homecare provides opportunities for improved cost savings and improved patient experience, but several issues have already been reported worldwide. Patient education, training, support, and regular supervision, as well as the competency of HCPs to manage these patients, have all been identified as factors that contribute to the success or failure of self-administration of parenteral therapy at home, which might impact treatment outcomes and adherence. This is an area that needs urgent research.

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Altered body image, disordered eating, and suboptimal glycaemic control in type 1 diabetes: Is technology and GLP1 agonists an option? (2024)

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Type of publication:
Conference abstract

Author(s):
*Basavaraju N.; *Jones M.; *Moulik P.

Citation:
British Journal of Diabetes. Conference: ABCD Diabetes Update. Loughborough United Kingdom. 24(1) (pp 112-113), 2024. Date of Publication: June 2024.

Abstract:
Introduction: Disordered eating in type 1 diabetes (T1DM) is associated with diabetes distress and suboptimal glycaemic control. We present a case of T1DM with binge eating disorder, discussing the benefits of GLP-1 analogues with continuous subcutaneous insulin infusion (CSII) therapy. Case: A 35-year-old female was diagnosed with T1DM in 2012, at 24 years of age, and commenced on basal bolus insulin. She had two pregnancies over the next seven years with good glycaemic control. There was pronounced dawn phenomenon post-pregnancy which was reflected in her erratic Freestyle Libre glucose readings. CSII therapy with Tandem T-slim was commenced a year later, in October 2020. Over the next 12-18 months, she was diagnosed with depression and hypertension, missed her outpatient diabetes clinic appointments, and struggled with diabetes management and fear of hypoglycaemia. During mid-2022 she developed mental health issues, with hallucinations and binge eating and a likely diagnosis of bipolar personality disorder. Later in the year, she was commenced on Tandem T-slim CSII and Dexcom G6 with Basal IQ technology. There was no evidence of retinopathy or neuropathy on annual diabetes screening. During outpatient diabetes review in February 2023, there was recurrent insulin pump auto-suspend followed by rebound hyperglycaemia and hence overnight basal insulin was reduced. Six months later, her weight had increased and glycaemic control worsened due to continued binge eating, missing pre-meal boluses, and she continued to be under the mental health liaison team. Her insulin was changed from Novorapid to Lyumjev (after discussion with the patient due to licensing criteria with the insulin pump) to accommodate binge eating hyperglycaemia and she was supported by motivational interviewing whilst awaiting review by eating disorders services. A month later, in October 2023, after CSII MDT discussion, she was commenced on control IQ – hybrid closed loop (HCL). In November 2023, her GMI (Glucose Management Indicator) improved, and she was commenced on dulaglutide after full discussion and patient consent including licensing criteria in T1DM. A month later, her food cravings reduced, she felt more positive about diabetes self-management and her insulin requirement reduced from 108 units to 98 units (basal 38%, bolus 62%). Her weight, BMI, HbA1c and ambulatory glucose profile data are shown in the Table. Discussion(s): HCL helped to improve glycaemic control by increasing TIR and reducing HbA1c. GLP-1 analogues have shown positive effects on reducing binge eating and weight loss. The combination of HCL and GLP-1 analogue in this patient resulted in lower insulin doses, positive attitude towards diabetes self-management along with improved clinical parameters and patient satisfaction. Binge eating disorders are associated with obesity and increase in cardiovascular risk. GLP-1 analogues in obese T1DM patients improve metabolic profile, weight, HbA1c and insulin requirement, with no increase in incidence of diabetic ketoacidosis or hypoglycaemia. There are no reported cases of T1DM with binge eating disorder on GLP-1 analogues in the literature and hence further studies are warranted.

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The option of transosseous distal suture placement during minimally invasive Achilles tendon repair for high-risk patients can improve outcomes, however does not prevent re-rupture (2024)

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Type of publication:
Journal article

Author(s):
*Carmont, Michael R; Nilsson-Helander, Katarina; Carling, Malin.

Citation:
BMC Musculoskeletal Disorders. 25(1):610, 2024 Aug 01.

Abstract:
PURPOSE: Achilles tendon ruptures (ATRs) close to the insertion, in high-level athletes, and in patients at high risk of re-rupture, may be better suited to operative repair. Minimally Invasive Repair (MIR) of the Achilles tendon has excellent outcome and low complication rates. Traditionally MIR has showed lower repair strength, failing due to suture pull-out from the distal tendon stump. The aim of this study was to describe the outcome of ATR patients who received transosseous distal suture placement using a standard technique as a reference. METHODS: Following ATR, patients were evaluated for pre-injury activity level, body weight, location of the tear and size of the distal Achilles tendon stump. Patients considered to be at high-risk of re-rupture: Tegner level >= 8, body weight >= 105Kg and distal ATR, received transosseous (TO) distal suture placement (n = 20) rather than the usual transtendinous (TT) technique (n = 55). Patient reported outcome measures and functional evaluation was performed at 12 months following repair. RESULTS: At 12 months follow up both methods resulted in good median (IQR) Achilles tendon Total Rupture Score TO 83.8 (74-88.3) vs. TT 90 (79-94), low increased relative Achilles Tendon Resting Angle TO -3.5 (3.6) vs. TT -3.5 (3.3) and mean (SD) Single leg Heel-Rise Height Index TO 88.2% (9.9) vs. TT 85.6% (9.9) (n.s.). There were 4 re-ruptures in the high-risk group and 2 in the group receiving TT distal suture placement. All but one of these were traumatic in nature. The mode of failure following TO distal suture placement was proximal suture pull out. CONCLUSIONS: To distal suture placement during minimally-invasive Achilles tendon repair for higher-risk patients can lead to results equivalent to those in lower-risk patients treated with a standard TT MIR technique, except for the re-rupture rate which remained higher. There may be factors that have greater influence on outcome other than suture placement following ATR.

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Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures (2024)

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Type of publication:
Journal article

Author(s):
Mahmood U; Blake A; Rathee S; Samuel L; Murray G; Sebag-Montefiore D; *Gollins S; West NP; Begum R; Bach SP; Richman SD; Quirke P; Redmond KL; Salto-Tellez M; Koelzer VH; Leedham SJ; Tomlinson I; Dunne PD; Buffa FM; Maughan TS; Domingo E

Citation:
Cancer Research Communications. 4(7):1765-1776, 2024 Jul 01.

Abstract:
Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826). Exploratory analyses were done with transcriptomic signatures for the endpoint of pathologic complete response (pCR), considering treatment regimen or CMS subtype. Relevant findings were tested for overall survival and recurrence-free survival. Immune and stromal signatures were strongly associated with pCR and lack of pCR, respectively, in RT and capecitabine (Cap)/5-fluorouracil (5FU)-treated patients (N = 387), in which the radiosensitivity signature (RSS) showed the strongest association. Upon addition of oxaliplatin (Ox; N = 123), stromal signatures switched direction and showed higher chances to achieve pCR than without Ox (p for interaction 0.02). Among Cap/5FU patients, most signatures performed similarly across CMS subtypes, except cytotoxic lymphocytes that were associated with pCR in CMS1 and CMS4 cases compared with other CMS subtypes (p for interaction 0.04). The only variables associated with survival were pCR and RSS. Although the frequency of pCR across different chemoradiation regimens is relatively similar, our data suggest that response rates may differ depending on the biological landscape of rectal cancer. Response to neoadjuvant RT in stroma-rich tumors may potentially be improved by the addition of Ox. RSS in preoperative biopsies provides predictive information for response specifically to neoadjuvant RT with 5FU. SIGNIFICANCE: Rectal cancers with stromal features may respond better to RT and 5FU/Cap with the addition of Ox. Within patients not treated with Ox, high levels of cytotoxic lymphocytes associate with response only in immune and stromal tumors. Our analyses provide biological insights about the outcome by different radiotherapy regimens in rectal cancer.

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Automating incidence and prevalence analysis in open cohorts (2024)

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Type of publication:
Journal article

Author(s):
Cockburn N.; Hammond B.; Gani I.; Cusworth S.; Acharya A.; Gokhale K.; Thayakaran R.; Crowe F.; Minhas S.; *Smith W.P.; Taylor B.; Nirantharakumar K.; Chandan J.S.;

Citation:
BMC medical research methodology. 24(1) (pp 144), 2024. Date of Publication: 04 Jul 2024.

Abstract:
MOTIVATION: Data is increasingly used for improvement and research in public health, especially administrative data such as that collected in electronic health records. Patients enter and exit these typically open-cohort datasets non-uniformly; this can render simple questions about incidence and prevalence time-consuming and with unnecessary variation between analyses. We therefore developed methods to automate analysis of incidence and prevalence in open cohort datasets, to improve transparency, productivity and reproducibility of analyses. IMPLEMENTATION: We provide both a code-free set of rules for incidence and prevalence that can be applied to any open cohort, and a python Command Line Interface implementation of these rules requiring python 3.9 or later. GENERAL FEATURES: The Command Line Interface is used to calculate incidence and point prevalence time series from open cohort data. The ruleset can be used in developing other implementations or can be rearranged to form other analytical questions such as period prevalence. AVAILABILITY: The command line interface is freely available from https://github.com/THINKINGGroup/analogy_publication .

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Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study (2024)

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Type of publication:
Journal article

Author(s):
Connor M.J.; Genie M.; Dudderidge T.; Wu H.; Sukumar J.; Beresford M.; Bianchini D.; Goh C.; Horan G.; Innominato P.; Khoo V.; Klimowska-Nassar N.; Madaan S.; Mangar S.; McCracken S.; Ostler P.; Paisey S.; Robinson A.; Rai B.; Sarwar N.; *Srihari N.; Jayaprakash K.T.; Varughese M.; Winkler M.; Ahmed H.U.; Watson V.

Citation:
European Urology Oncology. (no pagination), 2024. Date of Publication: 2024.

Abstract:
Background and objective: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. Method(s): A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. Key findings and limitations: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. Conclusions and clinical implications: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. Patient Summary: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

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