Effect of chemotherapy on quality of life in patients with non-small cell lung cancer.

PURPOSE: This study was conducted to evaluate the extent to which quality of life (QoL) assessment has been incorporated into clinical trials of patients with advanced non-small cell lung cancer (NSCLC) receiving palliative chemotherapy. PATIENTS AND METHODS: Phase III trials for patients with NSCLC treated with palliative chemotherapy were identified by a literature search of PubMed. All abstracts and relevant articles from August 1986 to October 2011 were reviewed. The primary focus was on (a) whether these articles had incorporated QoL as an endpoint, (c) what instruments were used to measure QoL and (c) impact of chemotherapy on QoL. RESULTS: There were 3,780 items indexed under 'quality of life and lung cancer'. One hundred three studies were identified which measured QoL using validated QoL instruments. Fifty-five of these trials assessed the effects of palliative chemotherapy on QoL in patients with advanced NSCLC. The European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire was the most widely used questionnaire; other commonly used measurement scales used were the Functional Assessment of Cancer Therapy-Lung and the Lung Cancer Symptom Scale. The majority of studies showed that chemotherapy had a positive impact on QoL and disease-specific symptoms. CONCLUSION: It is now widely accepted that QoL should be considered as a primary endpoint of treatment in patients with advanced lung cancer both in clinical practice and clinical trials to further define meaningful response. As the traditional outcome measures of survival and tumour response are poor in this population, QoL assessment may offer a more comprehensive approach to evaluating the relative risks and benefits associated with treatments.

Extreme Symptom Burden for Patients With COVID-19 at the End of Life; Extrapolation of Knowledge Gained to Achieve Sustained Comfort and Dignity for all Patients in Their Last Days of Life1.

BACKGROUND: We describe two complex cases in the setting of COVID-19 at the End of Life, to enhance learning for all patients. CASE PRESENTATION: Maintenance of sustained comfort in two cases required multiple drugs, specifically selected for symptoms that necessitated three separate pumps delivering continuous 24-hour subcutaneous infusion. CASE MANAGEMENT: Management of sustained comfort included opioid, midazolam, anti-secretory, diclofenac for intractable temperature, phenobarbital for extreme agitation, in one, where seizure activity was present, while insomnia, was a prominent feature of another. Management of Akatasia was also required. CASE OUTCOME: Attention to each individual patient's rapidly evolving symptoms, during the dying phase, with a thorough differential diagnosis, wa s vitally important in the context of a 'Good Death'. This was achieved in both cases, reflected by evidence at the bedside of comfort and a minimum need for 'as required' drugs in the last days of life. CONCLUSIONS: COVID-19 being a new illness, we need to prospectively study the symptom burden/clustering at End of Life and learn from management of this new disease for other illnesses also. Further research is required to develop protocols on; when does Midazolam dose reach tolerance and when should an alternative drug such as phenobarbital for sustained Gamma-Aminobutyric Acid effects be initiated; examine the optimal approach to sustained temperature control; be cognisant of extrapyramidal side effects of drugs used at End of Life and consider looking at a lack of need for 'as required' drugs in the last days of life as an outcome measure of sustained comfort.

Case Series of Akathisia in Palliative Medicine: Patient Perspective and Efficacy of Procyclidine in Diagnosis and Management.

AIMS: Akathisia is a disturbing, reversible but under-diagnosed extrapyramidal side effect of medications used in palliative medicine. We assessed patients' subjective experience of akathisia and response to procyclidine, an anticholinergic used to treat extrapyramidal effects. We also aimed to discuss future areas of research and alternatives to akathisia-causing medications. METHODS: Suitable patients were retrospectively identified by palliative medicine physicians in a tertiary hospital and a chart review was undertaken. Information gathered included the account of their experience of akathisia, use of inciting medications, treatment, and outcome. RESULTS: 20 patients were identified, 12 females, 8 males. Mean number of days on the inciting drug(s) to onset of akathisia symptoms was 18.1. Mean number of days from commencing inciting drug(s) to diagnosis was 20.9. Patients' descriptions revealed similarities including feeling "locked in" and a need to constantly move. One patient described a "glass coffin" enclosing her. 16 patients had full response to treatment with procyclidine, 3 had partial response requiring up-titration of dosing, response was not documented in 1. CONCLUSIONS: Akathisia is an elusive symptom that can have dramatic reversibility when treated. Lack of recognition causes unnecessary patient suffering. Procyclidine appears to aid diagnosis and be an effective treatment. Protocols to reduce incidence and guide diagnosis and management are proposed. Further studies are required, in which subjective outcome measures are used and medications to treat akathisia are studied. Recognition remains challenging, causing significant distress for palliative patients, for whom quality of life is paramount.

Investigating the effectiveness of oral ketamine on pain, mood and quality of life in treatment resistant chronic pain.

Introduction: Chronic pain is defined as pain lasting longer than 3 months. This often causes persistent emotional distress and functional disability that is refractory to conventional treatments. Emerging evidence suggests that oral Ketamine therapy may have a specific role in managing treatment-resistant chronic pain. This study aimed to assess the effectiveness of oral ketamine within a tertiary chronic pain management clinic. Methods: This study was a clinic-based retrospective descriptive study of 79 patients with a broad range of chronic pain diagnoses and treated with oral ketamine over a period up to 12 years. Changes in pain, mood and quality of life (QoL) were assessed using a numerical pain severity score, the Brief Pain Inventory (BPI), the Public Health Questionnaire (PHQ-9) and American Chronic Pain Association Quality of Life (QoL) scale. Results: 73 patients were accessible for follow-up (mean daily dose and treatment duration were 193.84 mg and 22.6 months respectively). Pain scores decreased (p < 0.0001) on both numerical scores (41.6% decrease) and BPI scoring (mean decrease 2.61). Mood improved (p < 0.0001) across both PHQ-9 and BPI measurements. Patients also reported less difficulty with daily activities and improved QoL. The most common adverse reaction was drowsiness (21.9%), with 30.1% reporting no adverse reactions from Ketamine. Discussion: This work adds to the growing body of evidence that under the supervision of a pain specialist, oral ketamine therapy may be a safe, tolerable and effective treatment for chronic pain conditions which have not responded to other management options. Further research is required to produce a more accurate understanding of its chronic use. Key message: This real-world study shows that patients being treated with oral ketamine for chronic pain report decreased severity of pain, improved mood and increased quality of life across all conditions.

Central anticholinergic syndrome from hyoscine hydrobromide in an unresponsive patient.

Terminal agitation is common and causes severe distress for patients and loved ones. Careful assessment is of paramount importance in identifying a cause. PA patient with gastric adenocarcinoma who was admitted with adverse effects post-chemotherapy deteriorated acutely with a presumed intracerebral event. Secretions were an issue and hyoscine hydrobromide was commenced. Within twenty-four hours, the patient became acutely agitated and did not respond to standard treatment.After careful clinical examination out-ruling other causes, toxic psychosis secondary to hyoscine hydrobromide was felt to be most likely. Rotating anti-secretories and commencing a phenobarbitone infusion to treat severe agitation resulted in prolonged comfort before death.Inhibiting cholinergic transmission at central muscarinic receptors can cause psychosis, delirium, etc. Hyoscine hydrobromide crosses the blood brain barrier. This case demonstrates that even in unresponsive patients, it may cause agitation. If standard therapies are failing to control agitation, all possibilities must be considered. Central side effects of hyoscine hydrobromide may be a rare but under-recognised cause of agitation. This case demonstrates how through careful clinical assessment of possible differentials, and prompt and effective management of the most likely causes of distress, lasting comfort can be achieved. Patient with gastric adenocarcinoma who was admitted with adverse effects post-chemotherapy deteriorated acutely with a presumed intracerebral event. Secretions were an issue and hyoscine hydrobromide was commenced. Within twenty-four hours, the patient became acutely agitated and did not respond to standard treatment.

Methadone prescribed as an analgesic by a specialist palliative medicine team in an acute hospital inpatient setting: retrospective study.

Emerging evidence suggests that methadone has a specific role in the management of treatment resistant cancer-related pain. OBJECTIVES: To investigate the utilisation pattern, safety and efficacy of methadone prescribed as an analgesic for the management of complex cancer-related pain in an acute hospital inpatient setting. METHODS: A retrospective longitudinal observational study of patients prescribed methadone as an analgesic between April 2020 and July 2021 was performed.Changes in coprescribed baseline opioid, use of breakthrough opioid analgesic, patient rated pain scores and adverse side effects were analysed. RESULTS: 16 patients with complex cancer-related treatment resistant pain who were prescribed methadone were included in the study. Of the 16 patients, 14 patients had metastatic disease. Pain was classified in 14 patients as mixed nociceptive-neuropathic and in 2 patients as neuropathic. 13 patients were coprescribed methadone with a pre-established opioid. Methadone was associated with a statistically significant decrease in both opioid breakthrough analgesic by 61%±28% (p<0.001), and coprescribed opioid by 17%±12% (p=0.015). Patient rated pain scores were also significantly decreased (p<0.001). CONCLUSION: Methadone appears to have a specific role in the management of complex cancer pain, neuropathic pain, opioid-tolerance and opioid-induced hyperalgesia, which may be attributable to N-methyl-D-aspartate receptor antagonism.

Mycobacterium goodii pneumonia: An unusual presentation of nontuberculous mycobacterial infection requiring a novel multidisciplinary approach to management.

BACKGROUND: Mycobacterium goodii is a rapidly growing nontuberculous mycobacterium which has been associated with several infections including cellulitis, osteomyelitis, lymphadenitis, infected pacemakers and bursitis but it is a rare cause of respiratory infection. CASE PRESENTATION: In this case report we describe a 51-year-old woman who presented with a 6-week history of non-productive cough, pleuritic chest pain and weight loss. She had a history of gastric adenocarcinoma managed with a distal oesophagectomy and total gastrectomy and consequentially suffered severe post-operative gastric reflux. Initial cultures were negative but following a VATS lung biopsy Mycobacterium goodii was cultured and histology revealed an organising pneumonia. Treatment was with a prolonged course of steroids, amikacin and meropenem followed by oral ciprofloxacin and doxycycline. Ongoing gastric dysmotility and weight loss showed clinical improvement with a novel approach of a combination of prokinetics and somatostatin analogues controlling risk of repeat aspiration and improving symptom control. CONCLUSIONS: This is an unusual case of organising pneumonia related to Mycobacterium goodii infection and highlights the importance of mycobacterial culture in unusual and unresolving cases of organising pneumonia. The importance of controlling symptoms related to gastric dysmotility and aspiration is also addressed.

Disturbing and distressing: a mixed methods study on the psychological impact of end of life care on junior doctors.

BACKGROUND: The Irish Medical Council has identified gaps in knowledge and communications skills of new-entrant doctors in legal, ethical and practical aspects of end of life care. AIMS: To determine the frequency with which junior doctors deal with end of life care and patient death and to evaluate the impact this has on their psychological wellbeing. DESIGN: A questionnaire was distributed to junior doctors to determine the frequency with which the participants had managed a patient at end of life. An abbreviated Posttraumatic Stress Disorder Checklist-Civilian version was used to evaluate psychological distress. Critical incident technique interviews explored the challenges of caring for patients at end of life. SETTING/PARTICIPANTS: A total of 110 junior doctors in two teaching hospitals in Ireland completed the questionnaire: 39 (35.5%) interns and 71 (64.5%) senior house officers. In addition, 31 interviews were carried out with interns, senior house officers and registrars. RESULTS: The majority (81.8%) had pronounced a death with 39.4% of senior house officers doing so more than 10 times. Three quarters (75.5%) had discussed end of life with a patient's family. Of the 110 respondents that completed the posttraumatic stress disorder checklist, 11.8% screened positively for posttraumatic stress disorder. Challenges identified at interview included lack of knowledge and preparedness, difficulty communicating with family members, a lack of support and a feeling of failure. CONCLUSIONS: Junior doctors are regularly carrying out tasks related to end of life care, resulting in high levels of psychological distress. Further training and a change in culture are required.

Status dystonicus due to missense variant in ARX: Diagnosis and management.

Movement disorders are increasingly identified in infantile encephalopathies due to single gene disorders (e.g. SCN2A, CDKL5, ARX). The associated movement disorder can be challenging to recognise and treat. We report a 2 year-old boy with a background history of Ohtahara syndrome due to a missense variant in ARX (the aristaless-related homeobox gene) who subsequently developed status dystonicus. ARX is a transcription factor that plays a critical role in cortical neuronal development and is associated with a range of important neurodevelopmental disorders depending on the site of the pathogenic variant. Cases of status dystonicus are described with variants affecting the polyalanine expansion region of ARX but have not been reported previously with variants affecting the aristaless domain of ARX as in this case. Dystonic episodes posed a challenge in recognition and treatment, including confusion with status epilepticus. We discuss the difficulties in diagnosis and management of status dystonicus, an underreported life-threatening emergency in children.

The measurement of response shift in patients with advanced prostate cancer and their partners.

BACKGROUND: There is increasing evidence to support the phenomenon of response shift (RS) in quality of life (QoL) studies, with many current QoL measures failing to allow for this. If significant response shift occurs amongst prostate cancer patients, it will be necessary to allow for this in the design of future clinical research and to reassess the conclusions of previous studies that have not allowed for this source of bias. This study therefore aimed to assess the presence of RS and psychosocial morbidity in patients with advanced prostate cancer and their partners. METHODS: 55 consecutive advanced prostate cancer patients and their partners completed the Prostate Cancer Patient & Partner questionnaire (PPP), shortly after diagnosis and again at 3 months and 6 months. At the follow-up visits, both patients and partners also completed a then-test in order to assess RS. RESULTS: Partners consistently showed greater psychological morbidity than patients in relation to the prostate cancer. This was most marked on the General Cancer Distress (GCD) subscale (p < 0.001, paired t-test), and regarding worries about treatment (p = 0.01). Significant RS was identified in partners and patients by the use of the then-test technique, particularly on the GCD subscale, the concerns about treatment and the concerns about urinary symptoms items. CONCLUSION: These results suggest the presence of RS in patients with advanced prostate cancer and their partners, with higher levels of psychosocial morbidity noted amongst partners. This is the first study to identify RS in partners and calls into question the interpretation of all studies assessing changes in QoL that fail to allow for this phenomenon.