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Statins as Potential Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating Repurposed Drugs (2021)

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Type of publication:
Journal article

Author(s):
Joharatnam-Hogan N, Alexandre L, Yarmolinsky J, *Lake B, *Capps N, Martin RM, Ring A, Cafferty F, Langley RE

Citation:
Current Oncology Reports, 13 Feb 2021, 23(3):29

Abstract:
Purpose of review: Repurposing established medicines for a new therapeutic indication potentially has important global and societal impact. The high costs and slow pace of new drug development have increased interest in more cost-effective repurposed drugs, particularly in the cancer arena. The conventional drug development pathway and evidence framework are not designed for drug repurposing and there is currently no consensus on establishing the evidence base before embarking on a large, resource intensive, potential practice changing phase III randomised controlled trial (RCT). Numerous observational studies have suggested a potential role for statins as a repurposed drug for cancer chemoprevention and therapy, and we review the strength of the cumulative evidence here.
Recent findings: In the setting of cancer, a potential repurposed drug, like statins, typically goes through a cyclical history, with initial use for several years in another disease setting, prior to epidemiological research identifying a possible chemo-protective effect. However, further information is required, including review of RCT data in the initial disease setting with exploration of cancer outcomes. Additionally, more contemporary methods should be considered, such as Mendelian randomization and pharmaco-epidemiological research with "target" trial design emulation using electronic health records. Pre-clinical and traditional observational data potentially support the role of statins in the treatment of cancer; however, randomised trial evidence is not supportive. Evaluation of contemporary methods provides little added support for the use of statin therapy in cancer. We provide complementary evidence of alternative study designs to enable a robust critical appraisal from a number of sources of the go/no-go decision for a prospective phase III RCT of statins in the treatment of cancer.

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Do the heel-rise test and isometric strength improve after Achilles tendon repair using Dresden technique? (2022)

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Type of publication:
Journal article

Author(s):
De la Fuente, Carlos; Henriquez, Hugo; *Carmont, Michael R; Huincahue, Javiera; Paredes, Tamara; Tapia, María; Araya, Juan Pablo; Díaz, Nicolás; Carpes, Felipe P

Citation:
Foot and ankle surgery : official journal of the European Society of Foot and Ankle Surgeons; Jan 2022, 28(1) pages 37-43

Abstract:
BACKGROUND Achilles' tendon ruptures result in impaired plantar flexion strength and endurance. It is interesting to know the plantar flexion strength, the number of heel-rise repetitions, and the maximal calf circumference following Achilles' tendon ruptures repair. METHODS Both the injured and non-injured legs of thirty male patients with Achilles' tendon ruptures treated with the percutaneous Dresden technique were compared with the ankle function of 30 healthy participants. Rehabilitation involved partial weight-bearing for three weeks and then increased to full weight-bearing and ankle exercises. RESULTS The injured legs had weaker plantar flexion strength (1.64 ± 0.17 Nm/kg) compared with the non-injured legs (1.91 ± 0.24 Nm/kg; p = 0.002) and the healthy participants' legs (1.93 ± 0.32 Nm/kg; p < 0.001). The non-injured leg had greater ability in doing heel-rise repetitions (39.4 ± 6.1 rep.) compared with the injured legs (37.2 ± 5.7 rep.; p < 0.023) and the healthy participants' legs (31.0 ± 13.0 rep.; p < 0.001). CONCLUSIONS The injured leg had not recovered full isometric strength but had improved heel-rise repetition.

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No difference in Achilles Tendon Resting Angle, Patient-reported outcome or Heel-rise height Index between Non- and Early-weightbearing the First Year after an Achilles Tendon Rupture (2020)

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Type of publication:
Journal article

Author(s):
*Carmont M; Brorsson, A.; Karlsson, J.; Nilsson-Helander, K.

Citation:
Muscles, Ligaments & Tendons Journal (MLTJ); Oct 2020; vol. 10 (no. 4); p. 651-658

Abstract:
Background. Patient-reported outcome scores and comparable re-rupture rates in randomized controlled trials have not shown a definitive benefit for operative treatment after acute Achilles tendon rupture. This, together with the increasing rupture rates in the older age group has led to non-operative treatment being increasingly used. Objective. This study aimed to determine the variation in Achilles Tendon Resting Angle (ATRA) together with patient reported and functional outcome, with non-operative management of the ruptured Achilles tendon using two different regimes, which have been shown to offer low re-rupture rates. Methods. This is a non-randomised cohort comparison of Achilles tendon rupture patients managed with Non-Weight-Bearing (NWB) for 6 weeks vs. Early Weight-Bearing (EWB). The NWB-group received a cast in plantar flexion for 2 weeks followed by 6 weeks in a controlled ankle motion boot with incremental diminishing plantar flexion. The EWB-group received an initial anterior protective plaster slab in plantar flexion followed by 6 weeks of weight-bearing on the meta-tarsal heads, with an anterior shell restricting dorsiflexion. Results. At 12 months after the injury there were no differences in any of the variables between the two treatment groups. The NWB-group compared to the EWB-group reported at mean (SD) for ATRA -9.8° (4.6°) versus -11.4° (5°), p=0.32, for Achilles tendon Total Rupture Score (ATRS) 87 (10) versus 79 (19), p=0.43 and for Heel-Rise Height Index (HRHI) 71% (19%) versus 59% (13%), p=0.13. Conclusions. The two methods of non-operative treatment studied lead to increased relative ATRA following injury, however, patients report only minor limitation in terms of outcome. Patients had almost a third less heel-rise height compared with the non-injured ankle.

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The correlation between bowel complications and cardiac surgery (2021)

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Type of publication:
Journal article

Author(s):
Mishra V.; Hewage S.; *Islam S.; Harky A.

Citation:
Scandinavian Journal of Surgery; Jun 2021; vol. 110 (no. 2); p. 187-192

Abstract:
Although advances in knowledge and technology have improved outcomes in surgical cardiac patients over the last decade, complications following cardiac operations still remain to be potentially fatal. Gastrointestinal complications, in particular, tend to have high rates of reintervention and mortality following cardiac surgery, with ischemia and hemorrhage being two of the commonest underlying causes. The intention of this review is to identify which risk factors play important roles in predisposing patients to such complications and to gain better insight into the pathogenesis of the sequelae. Furthermore, strategies for prevention have been discussed to educate and increase awareness of how adverse cardiac surgical outcomes can be minimized.

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Oral and maxillofacial surgery patient satisfaction with telephone consultations during the COVID-19 pandemic (2020)

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Type of publication:
Journal article

Author(s):
*Horgan T.J.; *Alsabbagh A.Y.; *McGoldrick D.M.; *Bhatia S.K.; *Messahel A.

Citation:
The British Journal of Oral & Maxillofacial Surgery; Apr 2021; vol. 59 (no. 3); p. 335-340

Abstract:
Due to the COVID-19 pandemic most oral and maxillofacial surgical (OMFS) units have moved to conducting patient consultations over the telephone. The aim of this study was to assess patients' satisfaction with telephone consultations during the COVID-19 pandemic. A retrospective survey was conducted of OMFS patients at our hospital who had telephone consultations between 1 April – 8 June 2020. The survey was conducted by independent interviewers and used the Generic Medical Interview Satisfaction Scale (G-MISS) along with a previously published additional questionnaire. Variables recorded included age, gender, theme of consultation, grade of clinician, and type of consultation. Statistical analysis was performed to assess for any differences between patient groups. The records of 150 consecutive patients were reviewed and 135 met inclusion criteria. A total of 109 patients completed the survey giving a response rate of 80.74%. The total G-MISS score for satisfaction was high, which indicates a high level of satisfaction among all patients. We found no statistical difference in satisfaction when comparing patients in terms of gender, age, theme of consultation, or level of clinician. A significant difference was found in compliance levels between review and new patients, with review patients demonstrating higher compliance levels (p=0.004). Overall, 83.48% of patients said they would be willing to have a telephone consultation in future. The majority of patients in this study reported high levels of satisfaction with telephone consultations. New patients reported lower levels of compliance which may suggest this type of consultation is less suited to telephone consultation.

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Coronavirus Disease 2019: the Pivotal Role of UK Clinical Oncology and the UK Coronavirus Cancer Monitoring Project (2021)

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Type of publication:
Journal article

Author(s):
*Best ; Starkey, T.; *Chatterjee, A.; Fackrell, D.; *Pettit, L.; *Srihari, N.; Tween, H.; Olsson-Brown, A.; Cheng, V.; Hughes, D.J.; Lee, A.J.X.; Purshouse, K.; Arnold, R.; UK Coronavirus Cancer Monitoring Project Team; Sivakumar, S.; Cazier, J.-B.; Lee, L.Y.W.

Citation:
Clinical Oncology; Jan 2021; vol. 33 (no. 1), e50-e53

Abstract:

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Lessons of the month: Co-infection with SARS-CoV-2 and influenza B virus in a patient with community-acquired pneumonia (2020)

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Type of publication:
Journal article

Author(s):
*Coutinho A.; *Riaz A.; *Makan A.; *Crawford E.; *Dev D.; *Srinivasan K.; *Ahmad N.; *Moudgil H.

Citation:
Clinical medicine (London, England); Nov 2020; vol. 20 (no. 6); e262–3

Abstract:
Why we only infrequently detect or report two or more respiratory viruses co-infecting an adult host is poorly understood. We report a rare case where influenza B and SARS-CoV-2 caused viral pneumonia in a 74-year-old man diagnosed during the UK winter epidemic/pandemic for these organisms and discuss concepts of co-infection.

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Emotional Resilience and Bariatric Surgical Teams: a Priority in the Pandemic (2021)

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Type of publication:
Journal article

Author(s):
Graham, Yitka; Mahawar, Kamal; *Riera, Manel; Islam, Omar; Bhasker, Aparna Ghovil; Wilson, Michael; Tahrani, Abd; Moize, Violeta; Leal, Angela; Hayes, Catherine

Citation:
Obesity Surgery; Apr 2021; vol. 31 (no. 4); p. 1887-1890

Abstract:
The infection control measures implemented as a result of COVID-19 led to a postponement of bariatric surgical procedures across many countries worldwide. Many bariatric surgical teams were in essence left without a profession, with many redeployed to other areas of clinical care and were not able to provide the levels of patient support given before COVID-19. As the pandemic continues, some restrictions have been lifted, with staff adjusting to new ways of working, incorporating challenging working conditions and dealing with continuing levels of stress. This article explores the concept of emotional labour, defined as 'inducing or suppressing feelings in order to perform one's work', and its application to multidisciplinary teams working within bariatric surgery, to offer insight into the mental health issues that may be affecting healthcare professionals working in this discipline.

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Managing hyperlipidaemia in patients with COVID-19 and during its pandemic: An expert panel position statement from HEART UK (2020)

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Type of publication:
Journal article

Author(s):
Iqbal Z.; Ho J.H.; France M.; Schofield J.; Nicholson K.; Soran H.; Adam S.; Durrington P.; Syed A.; Neely D.; Rees A.; Payne J.; Khatib R.; Cegla J.; Byrne C.; Qureshi N.; *Capps N.; Ferns G.; Datta D.; Pottle A.; Halcox J.; Krentz A.

Citation:
Atherosclerosis; Nov 2020; vol. 313 ; p. 126-136

Abstract:
The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19) has resulted in a pandemic. SARS-CoV-2 is highly contagious and its severity highly variable. The fatality rate is unpredictable but is amplified by several factors including advancing age, atherosclerotic cardiovascular disease, diabetes mellitus, hypertension and obesity. A large proportion of patients with these conditions are treated with lipid lowering medication and questions regarding the safety of continuing lipid-lowering medication in patients infected with COVID-19 have arisen. Some have suggested they may exacerbate their condition. It is important to consider known interactions with lipid-lowering agents and with specific therapies for COVID-19. This statement aims to collate current evidence surrounding the safety of lipid-lowering medications in patients who have COVID-19. We offer a consensus view based on current knowledge and we rated the strength and level of evidence for these recommendations. Pubmed, Google scholar and Web of Science were searched extensively for articles using search terms: SARS-CoV-2, COVID-19, coronavirus, Lipids, Statin, Fibrates, Ezetimibe, PCSK9 monoclonal antibodies, nicotinic acid, bile acid sequestrants, nutraceuticals, red yeast rice, Omega-3-Fatty acids, Lomitapide, hypercholesterolaemia, dyslipidaemia and Volanesorsen. There is no evidence currently that lipid lowering therapy is unsafe in patients with COVID-19 infection. Lipid-lowering therapy should not be interrupted because of the pandemic or in patients at increased risk of COVID-19 infection. In patients with confirmed COVID-19, care should be taken to avoid drug interactions, between lipid-lowering medications and drugs that may be used to treat COVID-19, especially in patients with abnormalities in liver function tests.

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Results of a randomized phase III study of dysphagia-optimized intensity modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT) in head and neck cancer (2020)

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Type of publication:
Conference abstract

Author(s):
Nutting C.; Rooney K.; Foran B.; *Pettit L.; Beasley M.; Finneran L.; Roe J.; Tyler J.; Roques T.; Cook A.; Petkar I.; Bhide S.; Srinivasan D.; Boon C.; De Winton E.; Frogley R.; Mertens K.; Emson M.; Hall E.

Citation:
Journal of Clinical Oncology; 2020; vol. 38 (no. 15)

Abstract:
Background: Most newly diagnosed oro-& hypopharngeal cancers (OPC, HPC) are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. CRUK/14/014 investigated if using Do-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Method(s): Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary&nodal tumour; 54Gy/30f to remaining pharyngeal subsite&nodal areas at risk of microscopic disease) or Do-IMRT. The volume of the superior∣dle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in Do-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site&AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints included local control. Result(s): 112 patients (56 S-IMRT, 56 Do-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&4 disease; 86% had concomitant chemotherapy only, 4% induction&concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was S-IMRT 49.8Gy (IQR 47.1-52.4) vs. Do-IMRT 28.4Gy (21.3-37.4), p < 0.0001; superior∣dle PCM dose was S-IMRT 57.2Gy (56.3-58.3) vs. Do-IMRT 49.7Gy (49.4-49.9), p < 0.0001. Do-IMRT had significantly higher MDADI scores: S-IMRT 70.3 (SD 17.3) vs. Do-IMRT 77.7 (16.1), p = 0.016. 3 local recurrences (1 S-IMRT, 2 Do-IMRT) have been reported. Conclusion(s): Do-IMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC.

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