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Proteasome inhibitors are the backbone of AL amyloidosis treatment – bortezomib being most widely used. Carfilzomib is a proteasome inhibitor licenced to treat multiple myeloma; autonomic and peripheral neuropathy are uncommon toxicities with carfilzomib. There is limited data on the use of carfilzomib in AL amyloidosis. Here, we report the results of a phase Ib dose-escalation study of Carfilzomib-Thalidomide-Dexamethasone (KTD) in relapsed/refractory AL amyloidosis. The trial registered 11 patients from 6 UK centres from September 2017 to January 2019; 10 patients received at least one dose of trial treatment. 80 adverse events were reported from 10 patients in the 1st three cycles. One patient experienced dose-limiting toxicity (acute kidney injury) at a dose of 45 mg/m2, and another patient had a SAR (fever). Five patients experienced an AE ≥ grade 3. There were no haematologic, infectious, or cardiac AE ≥ grade 3. The overall haematological response rate (ORR) at the end of three cycles of treatment was 60%. Carfilzomib 45 mg/m2 weekly can be safely given with thalidomide and dexamethasone. The efficacy and tolerability profile appears comparable to other agents in relapsed AL amyloidosis. These data provide a framework for further studies of carfilzomib combinations in AL amyloidosis. [ABSTRACT FROM AUTHOR]

We report the long-term upper limb disability, health-related quality of life (HRQoL), functional impairment, self-perception of appearance and prevalence of neuropathic pain in patients with upper limb thalidomide embryopathy in the United Kingdom. One-hundred and twenty-seven patients responded to our electronic questionnaire. Mean Quick Version of the Disabilities of Arm, Shoulder, and Hand score was 54.3 (SD 22.6). Median EuroQoL 5-Dimension 5-Likert index, Work and Social Adjustment Scale, Derriford Appearance Scale 24 and Neuropathic Pain Scale were 0.6 (IQR 0.4 to 0.7), 15.5 (IQR 8.0 to 23.5), 35.5 (IQR 28.0 to 50.5), and −0.8 (IQR −1.4 to 0.8), respectively. Thirty-three patients (26%) reported neuropathic pain. Finger changes associated with radial longitudinal deficiency were an independent predictor of more severe upper limb disability. Eighty-nine patients (70%) reported deteriorating HRQoL with increasing age. Patients with upper limb thalidomide embryopathy experience age-related worsening of symptoms and function, highlighting the need for ongoing specialist care and support. Level of evidence: IV [ABSTRACT FROM AUTHOR]

Purpose: As people living with thalidomide embryopathy (TE) are now entering their seventh decade, we examine the impact of ageing and the prevalence of comorbid health conditions reported in holistic needs assessments (HNAs) by individuals with TE, compare it with an age-matched sample of the general population, and explore the relationship between comorbidities and TE pattern of impairment., Materials and Methods: The HNA categories were mapped and compared to those of the Health Survey for England (HSE) and analysed across four impairment groups (A-D)., Results: 94% (392/415) of individuals with TE residing in the UK participated in the HNA and consented to a secondary analysis of the data. Less than 2% (5/392) reported no comorbidities; 94% reported nervous system problems; including pain, pins and needles and numbness. Individuals with TE reported a significantly greater number of health comorbidities, including musculoskeletal problems, than the age-matched HSE population., Conclusions: Individuals with TE report significantly more health and well-being concerns than the general population of a similar age. Long-term monitoring is needed to ensure that support and rehabilitation services can meet their evolving needs.

Tom Yendell, an artist based in Hampshire, England, provided the cover art for the Summer 2018 issue of The Open Journal of Occupational Therapy (OJOT). "Silk Flowers" is a mouth painting made from acrylic on silk. Born a bilateral congenital amputee, Tom has learned to use his toes the same ways others use their hands. Tom relies little on aids and adaptations in his everyday life. He believes learning to do things your own way is empowering. As a world-renowned mouth and foot painter, Tom is a living example of how barriers can be overcome by doing things differently. Through his art and charitable works, Tom applies his creative energy, organizational skill, and determination to inspire others to live life to the fullest. [ABSTRACT FROM AUTHOR]

The yellow card scheme was introduced in 1964 following the thalidomide disaster. It plays a vital role in ensuring the safety of drugs, with submissions by health professionals and the general public made on a voluntary, anonymous and confidential basis. This article looks at the process involved, what happens to the collected data and why submissions remain vital to ensure the efficacy of pharmaceutical drugs. [ABSTRACT FROM AUTHOR]

In the early 1960s children were born with birth defects as a result of expectant mothers taking prescription drug thalidomide during pregnancy. This article examines the activities of the Society for the Aid of Thalidomide Children the media scrutiny of the thalidomide scandal, and the dedicated House of Commons debate of 1972 to provide new insight into the relationship between the family, normality, and disability in 1960s and 1970s Britain. The thalidomide tragedy was pivotal in the establishment of the Family Fund in 1973, which was, significantly, made available to the families of all severely congenitally-handicapped children. I argue that the thalidomide case was instrumental in raising awareness of the role of families in the care of disabled children. Thalidomide triggered debates on, research of, and interest in families with handicapped children before the role of the family carer had itself been formally acknowledged. [ABSTRACT FROM AUTHOR]

WILKES E.A., SELBY A.L., COLE A.T., FREEMAN J.G., RENNIE M.J. & KHAN Z.H. (2011) European Journal of Cancer Care 20, 593-600 Poor tolerability of thalidomide in end-stage oesophageal cancer Oesophageal cancer cachexia is a significant clinical problem, resulting in excessive morbidity and mortality. In a pilot study, 10 patients with cachexia due to advanced cancer of the oesophagus gained weight, including lean tissue, after 14-day treatment with thalidomide. Here, we present randomised placebo controlled trial data over a 6-week period to test the hypothesis that thalidomide is superior to placebo in terms of weight gain in patients with cachexia caused by oesophageal cancer. Thalidomide, 200 mg daily, or an identical placebo was given to patients with advanced oesophageal cancer. Total body weight and lean body mass were assessed in addition to drug tolerability and performance indices. Thirty-four patients were recruited. Of these, six given thalidomide and 16 given placebo completed the protocol; all withdrawals were due to adverse drug reactions or complications of disease. Thalidomide showed no benefit over placebo in participants who completed the protocol. These data suggest that thalidomide is poorly tolerated in patients with advanced cancer of the oesophagus and may not ameliorate the progression of cachexia. In the absence of hard supportive evidence, off-licence treatment with thalidomide should be used with great caution as an adjunct to nutritional support in patients with advanced cancer. [ABSTRACT FROM AUTHOR]

Therapeutic Reviews aim to provide essential independent information for health professionals about drugs used in palliative and hospice care. The content is also available on www.palliativedrugs.com and will feature in future editions of the Hospice and Palliative Care Formulary USA and its British and Canadian counterparts. The series editors welcome feedback on the articles (hq@palliativedrugs.com). [ABSTRACT FROM AUTHOR]

This essay offers a background on the history of the approval and marketing of the first oral contraceptive pill, Enovid in the U.S. and Enavid in Great Britain and argues on the role of this pill in reshaping pharmacology, social perceptions of medication and the regulatory process for new drugs during the second half of the 20th-century. It explores the role of thalidomide during the drug approval process and in the debate about the safety and efficacy of drugs. Also examined are the law and regulations on drug approval process in both countries.

The article presents a discussion on the Thalidomide tragedy and its repercussions on business ethics, and moral and scientific responsibility of businesses. The tragedy was brought by the marketing of thalidomide under the tradename Distavel by the Great Britain-based Distillers Co. which the company claimed can be given safely to pregnant women. Reported adverse effects of the drug to the fetus prompted the company to announce the withdrawal of the drug from the market. The adverse effects of the drug include the birth of malformed and deformed babies.

The author reflects on the introduction of the Yellow Card Scheme (YCS) in 1964 in Great Britain and the success of its implementation. She mentions the goal of YCS to help the British government in monitoring the safety of all medical devices and medicines in the country. The importance of the social media as a valuable source of information about adverse drug reactions (ADR) is also emphasized.

Reports the campaign to reform the law on drug liability in Great Britain. Discussion on the compensation for thalidomide victims; Challenges in proving the inadequate testing of thalidomide before market distribution; Arguments on the strict liability for prescribed drugs.

Introduction and Objective Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible fibrotic disease with more than 5000 incident cases annually in UK. IPF related cough is present in 80% cases and is often refractory to current treatments. Cough has a significant impact on quality of life, causing sleep disturbance, difficulties at work and stress incontinence. A previously published prospective open label phase II trial of thalidomide for treatment of pulmonary fibrosis suggested that IPF associated cough responded well to thalidomide. We have been using thalidomideas an "off-license" indication for selected IPF patients. The objective of this study was to review our experience of using Thalidomide as treatment for cough in IPF . Methods Nine patients were referred to Nottingham Academic Interstitial Lung Disease clinic between 2009 and 2011 for assessment of their cough. A modified version of Leicester Cough Questionnaire was used, in conjunction with subjective symptoms, to clinically assess their cough. A trial of PPI (omeprazole 40 mg) and Prednisolone (10 mg) for 6 weeks was given to all subjects. Two were excluded as did not have significant cough, one patient declined thalidomide after initial screening. Results Six patients were treated with thalidomide. Four had IPF, one had Hypersensitivity Pneumonitis and one had fibrotic Cryptogenic Organising Pneumonia. 72% were males with mean age 69 years (range 51-88 years). The median pre-thalidomide cough score was 74.5 (IQR 13.25) and post treatment cough score was 51.5 (IQR 49.25). This was statistically significant (p=0.046). Three stopped thalidomide subsequent to rash. Two patients are currently stable with 50 mg once daily, and 1 with 50 mg alternate daily of thalidomide. Conclusion Our observation of a carefully selected cohort of patients suggests that thalidomide has potential for treatment of IPF associated cough. It works quickly (within days) as reflected both subjectively and objectively via questionnaire, even when prednisolone has failed. However, it does have a significant side-effect profile. Identification of thalidomide's mechanism of action may aid the development of novel, effective anti-tussive therapy for this debilitating aspect of IPF . We will assess this in randomised open label trial comparing thalidomide vs prednisolone for treatment of IPF associated cough. [ABSTRACT FROM AUTHOR]

Presents medical news briefs. Painkiller that has been linked to suicide which is being withdrawn from the UK; Chronic fatigue syndrome which has now been recognised as a real disorder by the Netherlands; News of an extra payment for thalidomide survivors; Recommendation in the US that men 65 to 75-years-old who smoke should undergo screening for abdominal aortic aneurysm; NICE guidelines on treatment of osteoporosis.

Examines the obstetric problems of the thalidomide children in Great Britain. Association between thalidomide and the absence or abnormalities of limbs; Increase of caesarean section rate; Difficulties in measuring the blood pressure of women.