palliative care
Olivia Newton-John, actress, singer, and advocate of so-called alternative medicine (SCAM) has died following a lengthy battle with breast cancer. Her husband announced her death yesterday: “Dame Olivia Newton-John (73) passed away peacefully at her Ranch in Southern California this morning, surrounded by family and friends,” the post read. “We ask that everyone please respect the family’s privacy during this very difficult time. Olivia has been a symbol of triumphs and hope for over 30 years sharing her journey with breast cancer. Her healing inspiration and pioneering experience with plant medicine continues with the Olivia Newton-John Foundation Fund, dedicated to researching plant medicine and cancer.” 
Olivia was born on 26 September 1948 in Cambridge, UK. She came from a remarkable family. Her maternal grandfather was the Nobel Prize-winning physicist Max Born. She was thus the niece of my late friend Gustav Born. Newton-John’s father was an MI5 officer on the Enigma project at Bletchley Park who took Rudolf Hess into custody during World War II. After the war, he became the headmaster of the Cambridgeshire High School for Boys. He then took up a post in Australia, and young Olivia grew up down under. After starting out as a singer, she had her breakthrough with the film ‘Grease’ which brought her world fame.
Olivia was first diagnosed with breast cancer over 30 years ago and became an outspoken advocate of SCAM. Her cancer came back twice, and in 2017, she was diagnosed to have bone metastases. Meanwhile, she had married John Easterling, the boss of a natural remedy company, in an Incan spiritual ceremony in Peru.
In 2017, she said, “I decided on my direction of therapies after consultation with my doctors and natural therapists and the medical team at my Olivia Newton-John Cancer Wellness and Research Centre in Melbourne”. The Olivia Newton-John Cancer Wellness & Research Centre is a treatment centre of Austin Health, an Australian public hospital. They say that “anyone with a referral from their doctor can be treated here, regardless of the stage of their treatment or insurance status. At the ONJ Centre your care is built around your individual needs. This includes your physical, psychological and emotional health. Every patient is surrounded by a multidisciplinary team of cancer specialists, allied health and wellbeing therapists. Your dedicated treatment team work together to guide you through your optimal treatment pathway. Learn more about the cancer treatments we deliver at the ONJ Centre, how we support you through your care, and find answers to commonly asked questions.”
Their therapies include acupuncture and several other alternatives used for palliation, but the site seems refreshingly free of false claims and quackery. On their website, they say that “palliative care assists patients who have a life limiting illness to be as symptom free as possible. We work with you to meet your emotional, spiritual and practical needs in a holistic way. Our support is also extended to your family and carers.”
Olivia Newton-John’s history with SCAM is revealing. It seems that, by initially using SCAM instead of conventional treatments for her breast cancer in 1992, she worsened her prognosis. When the cancer returned, she opted for the best conventional oncology on offer. Yet, her liking for SCAM had not disappeared. Since 2017, she seems to have used cannabis and other SCAMs as add-ons to conventional medicine. Sadly, she had learned her lesson too late: alternative cancer treatments are a dangerous myth.
This article almost left me speechless:
The back-to-back waves of the COVID-19 pandemic have made a devastating impact globally. The conventional healthcare system is going through serious pressure as cases of the disease continue to spread and the numbers of hospitalizations are increasing every moment. It is becoming hard and challenging because the hospital resources are limited in number as compared with the rate of daily hospitalizations. There are significant shortages of patient care facilities and medical care providers, and on top of that, conventional healthcare systems do not have any proven treatments for COVID-19 patients. Experimental drugs like hydroxychloroquine, followed by remdesivir, ritonavir/lopinavir, and favipiravir are being administered under emergency use authorization (EUA). There is evidence that these experimental medications are causing adverse drug reactions, thus claiming the lives of the hospitalized COVID-19 patients. And those patients who survive the EUA medications and hospitalizations are left with iatrogenic immunosuppressive states leading to increased susceptibility towards secondary life-threatening infections like fungal diseases. In this scenario, complementary and alternative medical systems (CAMS) are providing commendable results with negligible adverse effects or iatrogenic issues in patients with COVID-19. There are several clinical cases recorded and published by various independent homoeopathic doctors and researchers worldwide. But unfortunately, because of a biased medical model and greed for monopolies, these effective treatment methods are not given equal opportunity as their conventional counterparts.
I think the best way to react to this nonsense might be to remind us what the only RCT of homeopathy for COVID showed.
This randomized, double-blind, two-armed, parallel, single-center, placebo-controlled study investigated the effectiveness and safety of the homeopathic medicine, Natrum muriaticum LM2, for mild cases of COVID-19.
Participants aged > 18 years, with influenza-like symptoms and a positive COVID test were recruited and randomized (1:1) into two groups that received different treatments during a period of at-home isolation. One group received the homeopathic medicine Natrum muriaticum, prepared with the second degree of the fifty-millesimal dynamization (LM2; Natrum muriaticum LM2), while the other group received a placebo.
The primary endpoint was time until recovery from COVID-19 influenza-like symptoms. Secondary measures included a survival analysis of the number and severity of COVID-19 symptoms (influenza-like symptoms plus anosmia and ageusia) from a symptom grading scale that was informed by the participant, hospital admissions, and adverse events. Kaplan-Meier curves were used to estimate time-to-event (survival) measures.
Data from 86 participants were analyzed (homeopathy, n = 42; placebo, n = 44). There was no difference in time to recovery between the two groups (homeopathy, n = 41; placebo, n = 41; P = 0.56), nor in a sub-group that had at least 5 moderate to severe influenza-like symptoms at the beginning of monitoring (homeopathy, n = 15; placebo, n = 17; P = 0.06). Secondary outcomes indicated that a 50% reduction in symptom score was achieved significantly earlier in the homeopathy group (homeopathy, n = 24; placebo, n = 25; P = 0.04), among the participants with a basal symptom score ≥ 5. Moreover, values of restricted mean survival time indicated that patients receiving homeopathy might have improved 0.9 days faster during the first five days of follow-up (P = 0.022). Hospitalization rates were 2.4% in the homeopathy group and 6.8% in the placebo group (P = 0.62). Participants reported 3 adverse events in the homeopathy group and 6 in the placebo group.
The authors concluded that the results showed that Natrum muriaticum LM2 was safe to use for COVID-19, but there was no statistically significant difference in the primary endpoints of Natrum muriaticum LM2 and placebo for mild COVID-19 cases.
Another relevant study compared the antibody response of homeopathic and conventional vaccines and placebo in young adults. A placebo-controlled, double-blind RCT was conducted where 150 university students who had received childhood vaccinations were assigned to diphtheria, pertussis, tetanus, mumps, measles homeopathic vaccine, placebo, or conventional diphtheria, pertussis, tetanus (Tdap) and mumps, measles, rubella (MMR) vaccines. The primary outcome was a ≥ two-fold increase in antibodies from baseline following vaccination as measured by ELISA. Participants, investigators, study coordinators, data blood drawers, laboratory technicians, and data analysts were all blinded.
None of the participants in either the homeopathic vaccine or the placebo group showed a ≥ two-fold response to any of the antigens. In contrast, of those vaccinated with Tdap, 68% (33/48) had a ≥ two-fold response to diphtheria, 83% (40/48) to pertussis toxoid, 88% (42/48) to tetanus, and 35% (17/48) of those vaccinated with MMR had a response to measles or mumps antigens (p < 0.001 for each comparison of conventional vaccine to homeopathic vaccine or to placebo). There was a significant increase in geometric mean titres of antibody from baseline for conventional vaccine antigens (p < 0.001 for each), but none for the response to homeopathic antigens or placebo.
The authors concluded that homeopathic vaccines do not evoke antibody responses and produce a response that is similar to placebo. In contrast, conventional vaccines provide a robust antibody response in the majority of those vaccinated.
To give ‘equal opportunity’ to implausible therapies would, in my view, not merely be wrong, it would be scandalously unethical. The role of homeopathy in the prophylaxis and symptomatic management of COVID-19 or other infections is very easily described; it is:
zero,
nil,
nothing,
null,
naught,
zilch.
During their cancer treatment path, cancer patients use numerous drugs,e.g.:
- anticancer medications,
- supportive drugs,
- other prescribed medications,
- herbal remedies,
- other OTC products.
This puts them at risk of significant drug interactions (DIs).
This study describes potential DIs in cancer patients and their prevalence and predictors.
A cross-sectional study was carried out in two centers in the northern West Bank, Palestine. The Lexicomp® Drug Interactions tool (Lexi-Comp, Hudson OH, USA) was applied to check the potential DIs. In addition, the Statistical Package for the Social Sciences (SPSS) was used to show the results and find the associations.
The final analysis included 327 patients. Most of the participants were older than 50 years (61.2%), female (68.5%), and had a solid tumor (74.6%). The total number of potential DIs was 1753, including 1510 drug-drug interactions (DDIs), 24 drug-herb interactions, and 219 drug-food interactions. Importantly, the prevalence of DDIs was 88.1%. In multivariate analysis, the number of potential DDIs significantly decreased with the duration of treatment (p = 0.007), while it increased with the number of comorbidities (p < 0.001) and the number of drugs used (p < 0.001).
The authors concluded that they found a high prevalence of DIs among cancer patients. This required health care providers to develop a comprehensive protocol to monitor and evaluate DIs by improving doctor-pharmacist communication and supporting the role of clinical pharmacists.
What the investigators did not study was the possibility of herb-herb and herb-non-herbal supplement interactions. The reason for this is probably simple: we know too little about these areas to make reasonable judgments. But even in the absence of such considerations, the prevalence of DDIs among cancer patients was high (88.1%). This means that the vast majority of cancer patients had at least one potential DDI. Over half of them were classified as moderately severe or worse.
The lessons seem to be to:
- use only truly necessary drugs and omit all remedies that are of doubtful value,
- educate the public about the risks of interactions,
- be skeptical about the messages of integrative medicine,
- consult a healthcare professional who is competent to make such judgments,
- conduct more rigorous research to increase our knowledge in this complex area.
Given the high prevalence of burdensome symptoms in palliative care (PC) and the increasing use of so-called alternative medicine (SCAM) therapies, research is needed to determine how often and what types of SCAM therapies providers recommend to manage symptoms in PC.
This survey documented recommendation rates of SCAM for target symptoms and assessed if, SCAM use varies by provider characteristics. The investigators conducted US nationwide surveys of MDs, DOs, physician assistants, and nurse practitioners working in PC.
Participants (N = 404) were mostly female (71.3%), MDs/DOs (74.9%), and cared for adults (90.4%). Providers recommended SCAM an average of 6.8 times per month (95% CI: 6.0-7.6) and used an average of 5.1 (95% CI: 4.9-5.3) out of 10 listed SCAM modalities. Respondents recommended mostly:
- mind-body medicines (e.g., meditation, biofeedback),
- massage,
- acupuncture/acupressure.
The most targeted symptoms included:
- pain,
- anxiety,
- mood disturbances,
- distress.
Recommendation frequencies for specific modality-for-symptom combinations ranged from little use (e.g. aromatherapy for constipation) to occasional use (e.g. mind-body interventions for psychiatric symptoms). Finally, recommendation rates increased as a function of pediatric practice, noninpatient practice setting, provider age, and proportion of effort spent delivering palliative care.
The authors concluded that to the best of our knowledge, this is the first national survey to characterize PC providers’ SCAM recommendation behaviors and assess specific therapies and common target symptoms. Providers recommended a broad range of SCAM but do so less frequently than patients report using SCAM. These findings should be of interest to any provider caring for patients with serious illness.
Initially, one might feel encouraged by these data. Mind-body therapies are indeed supported by reasonably sound evidence for the symptoms listed. The evidence is, however, not convincing for many other forms of SCAM, in particular massage or acupuncture/acupressure. So encouragement is quickly followed by disappointment.
Some people might say that in PC one must not insist on good evidence: if the patient wants it, why not? But the point is that there are several forms of SCAMs that are backed by good evidence for use in PC. So, why not follow the evidence and use those? It seems to me that it is not in the patients’ best interest to disregard the evidence in medicine – and this, of course, includes PC.
The Lancet is a top medical journal, no doubt. But even such journals can make mistakes, even big ones, as the Wakefield story illustrates. But sometimes, the mistakes are seemingly minor and so well hidden that the casual reader is unlikely to find them. Such mistakes can nevertheless be equally pernicious, as they might propagate untruths or misunderstandings that have far-reaching consequences.
A recent Lancet paper might be an example of this phenomenon. It is entitled “Management of common clinical problems experienced by survivors of cancer“, unquestionably an important subject. Its abstract reads as follows:
_______________________
Improvements in early detection and treatment have led to a growing prevalence of survivors of cancer worldwide.
Models of care fail to address adequately the breadth of physical, psychosocial, and supportive care needs of those who survive cancer. In this Series paper, we summarise the evidence around the management of common clinical problems experienced by survivors of adult cancers and how to cover these issues in a consultation. Reviewing the patient’s history of cancer and treatments highlights potential long-term or late effects to consider, and recommended surveillance for recurrence. Physical consequences of specific treatments to identify include cardiac dysfunction, metabolic syndrome, lymphoedema, peripheral neuropathy, and osteoporosis. Immunotherapies can cause specific immune-related effects most commonly in the gastrointestinal tract, endocrine system, skin, and liver. Pain should be screened for and requires assessment of potential causes and non-pharmacological and pharmacological approaches to management. Common psychosocial issues, for which there are effective psychological therapies, include fear of recurrence, fatigue, altered sleep and cognition, and effects on sex and intimacy, finances, and employment. Review of lifestyle factors including smoking, obesity, and alcohol is necessary to reduce the risk of recurrence and second cancers. Exercise can improve quality of life and might improve cancer survival; it can also contribute to the management of fatigue, pain, metabolic syndrome, osteoporosis, and cognitive impairment. Using a supportive care screening tool, such as the Distress Thermometer, can identify specific areas of concern and help prioritise areas to cover in a consultation.
_____________________________
You can see nothing wrong? Me neither! We need to dig deeper into the paper to find what concerns me.
In the actual article, the authors state that “there is good evidence of benefit for … acupuncture …”[1]; the same message was conveyed in one of the tables. In support of these categorical statements, the authors quote the current Cochrane review entitled “Acupuncture for cancer pain in adults”. Its abstract reads as follows:
Background: Forty per cent of individuals with early or intermediate stage cancer and 90% with advanced cancer have moderate to severe pain and up to 70% of patients with cancer pain do not receive adequate pain relief. It has been claimed that acupuncture has a role in management of cancer pain and guidelines exist for treatment of cancer pain with acupuncture. This is an updated version of a Cochrane Review published in Issue 1, 2011, on acupuncture for cancer pain in adults.
Objectives: To evaluate efficacy of acupuncture for relief of cancer-related pain in adults.
Search methods: For this update CENTRAL, MEDLINE, EMBASE, PsycINFO, AMED, and SPORTDiscus were searched up to July 2015 including non-English language papers.
Selection criteria: Randomised controlled trials (RCTs) that evaluated any type of invasive acupuncture for pain directly related to cancer in adults aged 18 years or over.
Data collection and analysis: We planned to pool data to provide an overall measure of effect and to calculate the number needed to treat to benefit, but this was not possible due to heterogeneity. Two review authors (CP, OT) independently extracted data adding it to data extraction sheets. Data sheets were compared and discussed with a third review author (MJ) who acted as arbiter. Data analysis was conducted by CP, OT and MJ.
Main results: We included five RCTs (285 participants). Three studies were included in the original review and two more in the update. The authors of the included studies reported benefits of acupuncture in managing pancreatic cancer pain; no difference between real and sham electroacupuncture for pain associated with ovarian cancer; benefits of acupuncture over conventional medication for late stage unspecified cancer; benefits for auricular (ear) acupuncture over placebo for chronic neuropathic pain related to cancer; and no differences between conventional analgesia and acupuncture within the first 10 days of treatment for stomach carcinoma. All studies had a high risk of bias from inadequate sample size and a low risk of bias associated with random sequence generation. Only three studies had low risk of bias associated with incomplete outcome data, while two studies had low risk of bias associated with allocation concealment and one study had low risk of bias associated with inadequate blinding. The heterogeneity of methodologies, cancer populations and techniques used in the included studies precluded pooling of data and therefore meta-analysis was not carried out. A subgroup analysis on acupuncture for cancer-induced bone pain was not conducted because none of the studies made any reference to bone pain. Studies either reported that there were no adverse events as a result of treatment, or did not report adverse events at all.
Authors’ conclusions: There is insufficient evidence to judge whether acupuncture is effective in treating cancer pain in adults.
This conclusion is undoubtedly in stark contrast to the categorical statement of the Lancet authors: “there is good evidence of benefit for … acupuncture …“
What should be done to prevent people from getting misled in this way?
- The Lancet should correct the error. It might be tempting to do this by simply exchanging the term ‘good’ with ‘some’. However, this would still be misleading, as there is some evidence for almost any type of bogus therapy.
- Authors, reviewers, and editors should do their job properly and check the original sources of their quotes.
PS
In case someone argued that the Cochrane review is just one of many, here is the conclusion of an overview of 15 systematic reviews on the subject: The … findings emphasized that acupuncture and related therapies alone did not have clinically significant effects at cancer-related pain reduction as compared with analgesic administration alone.
Barrie R. Cassileth died on Feb. 26 at an assisted-living home in Beverly Hills, California. I knew about Barrie because she was the 1st author of a most remarkable study published in 1991 in the prestigious NEJM. Here is the abstract:
Background: Cancer treatments without proved efficacy have achieved new levels of popularity, particularly among well-educated patients. The value of these therapies is vigorously debated.
Methods: We compared the length of survival and quality of life in patients who received treatment at a prominent unorthodox cancer clinic in addition to conventional treatment and in matched control patients from an academic cancer center who received only conventional treatment. All the patients had documented extensive malignant disease associated with a predicted median survival time of less than one year. The study sample consisted of 78 pairs of patients matched according to sex, race, age, diagnosis, and time from the diagnosis of metastatic or recurrent disease, who were enrolled over a period of 3 1/2 years. Periodic follow-up (approximately every two months) continued until death.
Results: There was no difference between the two patient groups in length of survival. Median survival for both groups was 15 months (P = 0.22; relative risk, 1.23; 95 percent confidence interval, 0.88 to 1.72). Quality-of-life scores were consistently better among conventionally treated patients from enrollment on.
Conclusions: For this sample of patients with extensive disease and for this particular unorthodox treatment regimen, conventional and unorthodox treatments produced similar results. 
In 1995, I met her for the first time when we both served on an NIH panel, and we kept in contact. When I had flown to Boston for a conference she even drove from New York to see me and have a chat. In 1998, she asked me to come to New York because she needed to discuss something important with me and wanted my advice. It turned out that she had been offered to create the Integrative Medicine Service at Memorial Sloan Kettering Cancer Center in New York sponsored by Laurance Rockefeller. She was very much in two minds about accepting. Her fear was that she would have to become an advocate of alternative medicine. I tried to reassure her and pointed out that I did not exactly turn into an advocate after accepting the Exeter post.
In the end, she accepted and, in the years that followed, we met several times at conferences, became friends, and published a few papers together. I even persuaded her to come to one of our annual conferences at Exeter as a keynote speaker. By then, she had clearly become an advocate of complementary medicine.
What had happened?
Barrie was very keen to differentiate alternative from complementary therapies in cancer care. The former she sharply condemned, while advocating the latter for improving the quality of life of cancer patients. When we discussed these issues, I argued that the ‘alternative versus complementary’ was a somewhat artificial division and that the overlap was large. I also pointed out that some of the complementary treatments she was backing were not based on good evidence. In other words, our views had begun to differ. We remained friends but gradually drifted apart and eventually lost contact.
Barrie Joyce Rabinowitz was born on April 22, 1938, in Philadelphia. She attended Bennington College in Vermont and spent a summer teaching art in Pownal, Massachusetts. She graduated with a degree in social sciences in 1959, a year after marrying Peter Cassileth. Barrie received a master’s degree in psychology from Albert Einstein University and a Ph.D. in medical sociology in 1978 from the University of Pennsylvania, where Peter Cassileth was an oncologist. As part of her doctoral program, Barrie worked closely with adult leukemia patients. After being hired at Pennsylvania as an assistant professor, she helped establish one of the first palliative cancer care programs in the US. Before accepting the post at Slone-Kettering, she taught at Duke, Harvard, and the University of North Carolina. In 2003, she became the founding president of the Society for Integrative Oncology.
While at Slone-Kettering, Barrie published several excellent books and high-quality studies of complementary medicine. She kept on working well after the normal retirement age. Her last RCT was only published in 2018. Here is the abstract:
Purpose: Approximately 20% of breast cancer survivors develop breast cancer-related lymphedema (BCRL), and current therapies are limited. We compared acupuncture (AC) to usual care wait-list control (WL) for treatment of persistent BCRL.
Methods: Women with moderate BCRL lasting greater than six months were randomized to AC or WL. AC included twice weekly manual acupuncture over six weeks. We evaluated the difference in circumference and bioimpedance between affected and unaffected arms. Responders were defined as having a decrease in arm circumference difference greater than 30% from baseline. We used analysis of covariance for circumference and bioimpedance measurements and Fisher’s exact to determine the proportion of responders.
Results: Among 82 patients, 73 (89%) were evaluable for the primary endpoint (36 in AC, 37 in WL). 79 (96%) patients received lymphedema treatment before enrolling in our study; 67 (82%) underwent ongoing treatment during the trial. We found no significant difference between groups for arm circumference difference (0.38 cm greater reduction in AC vs. WL, 95% CI – 0.12 to 0.89, p = 0.14) or bioimpedance difference (1.06 greater reduction in AC vs. WL, 95% CI – 5.72 to 7.85, p = 0.8). There was also no difference in the proportion of responders: 17% AC versus 11% WL (6% difference, 95% CI – 10 to 22%, p = 0.5). No severe adverse events were reported.
Conclusions: Our acupuncture protocol appeared to be safe and well tolerated. However, it did not significantly reduce BCRL in pretreated patients receiving concurrent lymphedema treatment. This regimen does not improve upon conventional lymphedema treatment for breast cancer survivors with persistent BCRL.
Her contribution to our knowledge about complementary therapies is outstanding, and I am sure that her papers will be cited for decades to come. She will be missed and remembered as an innovator in the field of palliative cancer care.
Barrie had been married three times. Her third husband, Richard Cooper, who was the Director of the Center for the Future of the Healthcare Workforce and a Senior Fellow in the Leonard Davis Institute of Health Economics at the University of Pennsylvania, died in 2016. Barrie is survived by her siblings, Stephen and Ruth Rabinowitz; her daughters, Jodi Cassileth Greenspan and Wendy Cassileth; her son, Gregory Cassileth; and 6 grandchildren.
