Turmeric is certainly a plant with fascinating properties; we have therefore discussed it before. Reseach into turmeric continues to be active, and I will continue to report about new studies.
This study was aimed at estimating the effect of turmeric supplementation on quality of life (QoL) and haematological parameters in breast cancer patients who were on Paclitaxel chemotherapy. In this case series with 60 participants, QoL was assessed using a standard questionnaire and haematological parameters were recorded from the patients’ hospital records.
Turmeric supplementation for 21 days resulted in clinically relevant and statistically significant improvement in global health status, symptom scores (fatigue, nausea, vomiting, pain, appetite loss, insomnia), and haematological parameters.
The authors concluded that turmeric supplementation improved QoL, brought about symptom palliation and increased hematological parameters in breast cancer patients.
The way the conclusions are phrased, they clearly imply that turmeric caused the observed outcomes. How certain can we be that this is true?
On a scale of 0 -10, I would say 0.
Because there are important other determinants of the outcomes:
- concommittant treatments,
- natural history,
- etc., etc.
Why does this matter?
- Because such unwarranted conclusions mislead patients, healthcare professionals and carers.
- Because such bad science gives a bad name to clinical research.
- Because this type of nonsense might deter meaningful research into a promising subject.
- Because no ‘scientific’ journal should be permitted to publish such nonsense.
- Because it is unethical of ‘scientists’ to make false claims.
But maybe the Indian authors are just a few well-meaning and naive practitioners who merely were doing their unexperienced best? Sadly not! The authors of this paper give the following affiliations:
- Clinical Pharmacology, Pfizer Healthcare Private Limited, Chennai, Tamil Nadu, India.
- Department of Radiation Oncology, Faculty of Medicine, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu, India.
- Process Development, HCL Technologies, Chennai, Tamil Nadu, India.
- Department of Pharmacognosy, Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, Tamil Nadu, India.
Yes, they really should know better!
There are of course 2 types of osteopaths: the US osteopaths who are very close to real doctors, and the osteopaths from all other countries who are practitioners of so-called alternative medicine. This post, as all my posts on this subject, is about the latter category.
I was alerted to a paper entitled ‘Osteopathy under scrutiny’. It goes without saying that I thought it relevant; after all, scrutinising so-called altermative medicine (SCAM), such as osteopathy is one of the aims of this blog. The article itself is in German, but it has an English abstract:
Osteopathic medicine is a medical specialty that enjoys a high level of recognition and increasing popularity among patients. High-quality education and training are essential to ensure good and safe patient treatment. At a superficial glance, osteopathy could be misunderstood as a myth; accurately considered, osteopathic medicine is grounded in medical and scientific knowledge and solid theoretical and practical training. Scientific advances increasingly confirm the empirical experience of osteopathy. Although more studies on its efficacy could be conducted, there is sufficient evidence for a reasonable application of osteopathy. Current scientific studies show how a manually executed osteopathic intervention can induce tissue and even cellular reactions. Because the body actively responds to environmental stimuli, osteopathic treatment is considered an active therapy. Osteopathic treatment is individually applied and patients are seen as an integrated entity. Because of its typical systemic view and scientific interpretation, osteopathic medicine is excellently suited for interdisciplinary cooperation. Further work on external evidence of osteopathy is being conducted, but there is enough knowledge from the other pillars of evidence-based medicine (EBM) to support the application of osteopathic treatment. Implementing careful, manual osteopathic examination and treatment has the potential to cut healthcare costs. To ensure quality, osteopathic societies should be intimately involved and integrated in the regulation of the education, training, and practice of osteopathic medicine.
This does not sound as though the authors know what scutiny is. In fact, the abstract reads like a white-wash of quackery. Why might this be so? To answer this question, we need to look no further than to the ‘conflicts of interest’ where the authors state (my translation): K. Dräger and R. Heller state that, in addition to their activities as further education officers/lecturers for osteopathy (Deutsche Ärztegesellschaft für Osteopathie e. V. (DÄGO) and the German Society for Osteopathic Medicine e. V. (DGOM)) there are no conflicts of interest.
But, to tell you the truth, the article itself is worse, much worse that the abstract. Allow me to show you a few quotes (all my [sometimes free] translations).
- Osteopathic medicine is a therapeutic method based on the scientific findings from medical research.
- [The osteopath makes] diagnostic and therapeutic movements with the hands for evaluating limitations of movement. Thereby, a blocked joint as well as a reduced hydrodynamic or vessel perfusion can be identified.
- The indications of osteopathy are comparable to those of general medicine. Osteopathy can be employed from the birth of a baby up to the palliative care of a dying patient.
- Biostatisticians have recognised the weaknesses of RCTs and meta-analyses, as they merely compare mean values of therapeutic effects, and experts advocate a further evidence level in which statictical correlation is abandonnened in favour of individual causality and definition of cause.
- In ostopathy, the weight of our clinical experience is more important that external evidence.
- Research of osteopathic medicine … the classic cause/effect evaluation cannot apply (in support of this statement, the authors cite a ‘letter to the editor‘ from 1904; I looked it up and found that it does in no way substantiate this claim)
- Findings from anatomy, embryology, physiology, biochemistry and biomechanics which, as natural sciences, have an inherent evidence, strengthen in many ways the plausibility of osteopathy.
- Even if the statistical proof of the effectiveness of neurocranial techniques has so far been delivered only in part, basic research demonstrates that the effects of traction or compression of bogily tissue causes cellular reactions and regulatory processes.
What to make of such statements? And what to think of the fact that nowhere in the entire paper even a hint of ‘scrutiny’ can be detected? I don’t know about you, but for me this paper reflects very badly on both the authors and on osteopathy as a whole. If you ask me, it is an odd mixture of cherry-picking the evidence, misunderstanding science, wishful thinking and pure, unadulterated bullshit.
You urgently need to book into a course of critical thinking, guys!
Many experts doubt that acupuncture generates the many positive health effects that are being claimed by enthusiasts. Yet, few consider that acupuncture might not be merely useless but could even make things worse. Here is a trial that seems to suggest exactly that.
This study evaluated whether combining two so-called alternative medicines (SCAMs), acupuncture and massage, reduce postoperative stress, pain, anxiety, muscle tension, and fatigue more than massage alone.
Patients undergoing autologous tissue breast reconstruction were randomly assigned to one of two postoperative SCAMs for three consecutive days. All participants were observed for up to 3 months. Forty-two participants were recruited from January 29, 2016 to July 11, 2018. Twenty-one participants were randomly assigned to massage alone and 21 to massage and acupuncture. Stress, anxiety, relaxation, nausea, fatigue, pain, and mood (score 0-10) were measured at enrollment before surgery and postoperative days 1, 2, and 3 before and after the intervention. Patient satisfaction was evaluated.
Stress decreased from baseline for both Massage-Only Group and Massage+Acupuncture Group after each treatment intervention. Change in stress score from baseline decreased significantly more in the Massage-Only Group at pretreatment and posttreatment. After adjustment for baseline values, change in fatigue, anxiety, relaxation, nausea, pain, and mood scores did not differ between groups. When patients were asked whether they would recommend the study, 100% (19/19) of Massage-Only Group and 94% (17/18) of Massage+Acupuncture Group responded yes.
The authors concluded tha no additive beneficial effects were observed with addition of acupuncture to massage for pain, anxiety, relaxation, nausea, fatigue, and mood. Combined massage and acupuncture was not as effective in reducing stress as massage alone, although both groups had significant stress reduction. These findings indicate a need for larger studies to explore these therapies further.
I recently went to the supermarket to find out whether combining two bank notes (£10 + £5) can buy more goods than one £10 note alone. What I found was interesting: the former did indeed purchase more than the latter. Because I am a scientist, I did not stop there; I went to a total of 10 shops and my initial finding was confirmed each time: A+B results in more than A alone.
It stands to reason that the same thing happens with clinical trials. We even tested this hypothesis in a systematic review entitled ‘A trial design that generates only ”positive” results‘. Here is our abstract:
In this article, we test the hypothesis that randomized clinical trials of acupuncture for pain with certain design features (A + B versus B) are likely to generate false positive results. Based on electronic searches in six databases, 13 studies were found that met our inclusion criteria. They all suggested that acupuncture is effective (one only showing a positive trend, all others had significant results). We conclude that the ‘A + B versus B’ design is prone to false positive results and discuss the design features that might prevent or exacerbate this problem.
But why is this not so with the above-mentioned study?
Why is, in this instance, A even more that A+B?
There are, of course, several possible answers. To use my supermarket example again, the most obvious one is that B is not a £5 note but a negative amount, a dept note, in other words: A + B can only be less than A alone, if B is a minus number. In the context of the clinical trail, this means acupuncture must have caused a negative effect.
But is that possible? Evidently yes! Many patients don’t like needles and experience stress at the idea of a therapist sticking one into their body. Thus acupuncture would cause stress, and stress would have a negative effect on all the other parameters quantified in the study (pain, anxiety, muscle tension, and fatigue).
My conclusion: in certain situations, acupuncture is more than just useless; it makes things worse.
The issue of informed consent has made regular appearances on this blog. It is important and has many intriguing aspects, particularly for so-called alternative medicine (SCAM). On the one hand, it is a ‘conditio sine qua non’ for any form of healthcare, while, on the other hand, it is a near impossibility in SCAM practice.
In this new article published in a chiro-journal, the authors review the origins of informed consent and trace the duty of disclosure and materiality through landmark medical consent cases in four common law (case law) jurisdictions. The duty of disclosure has evolved from a patriarchal exercise to one in which patient autonomy in clinical decision making is paramount. Passing time has seen the duty of disclosure evolve to include non-medical aspects that may influence the delivery of care. The authors argue that a patient cannot provide valid informed consent for the removal of vertebral subluxation. Further, vertebral subluxation care cannot meet code of conduct standards because it lacks an evidence base and is practitioner-centered.
The uptake of the expanded duty of disclosure has been slow and incomplete by practitioners and regulators. The expanded duty of disclosure has implications, both educative and punitive for regulators, chiropractic educators and professional associations. The authors discuss how practitioners and regulators can be informed by other sources such as consumer law. For regulators, reviewing and updating informed consent requirements is required. For practitioners it may necessitate disclosure of health status, conflict of interest when recommending “inhouse” products, recency of training after attending continuing professional development, practice patterns, personal interests and disciplinary findings.
The authors conclude that, ultimately such matters are informed by the deliberations of the courts. It is our opinion that the duty of a mature profession to critically self-evaluate and respond in the best interests of the patient before these matters arrive in court.
In their paper, the authors also provide a standard list of items required for ‘informed’ consent:
(1) emphasizing the patient’s role in shared decision-making
(2) disclosure of information
a. explaining the patient’s medical status including diagnosis and prognosis
b. describing the proposed diagnostic and therapeutic intervention, including the likelihood and effect of associated risks and benefits of the proposed action, including material risks
c. discussing alternatives to the proposed intervention, including doing nothing
(3) prompting and answering patient questions related to the proposed course of action (NB. this involves probing for understanding, not simply asking ‘do you have any questions’), and
(4) eliciting the patient’s preference (usually by signature). (NB. A signed form is not consent. The conversation between the clinician and the patient or carer is the true process of obtaining informed consent. The signature on the consent form is proof that the conversation took place and that the patient understood and agreed.)
The authors of this article – I do commend it to all chiropractors – take a mostly judicial view of informed consent (for an ethical perspective on the subject, I recommend our book). They do not discuss, whether chiropractors do, in fact, adhere to the ethical imperative of informed consent. As I have stated before, there is not much research on this issue. But the little that does exist fails to show that chiropractors care much about it.
If it’s an ethical imerative, why do chiropractors not abide by it?
The answer to this question is not difficult to find. Just imagine a conversation between a chiropractor (C) and a patient with neck pain (P):
- P: What’s your diagnisis?
- C: You are suffering from acute neck pain.
- P: Thanks, that much was clear to me. What do you suggest I do?
- C: I will perform a manipulation of your neck, if you agree.
- P: Why would this help?
- C: It can realign the vertebrae that are out of place, simply put.
- P: And my pain will disappear?
- C: Sometimes it does, yes.
- P: But will it disappear quicker than without manipulation.
- C: Some of the evidence says so.
- P: Ok, but what does the most reliable evidence say?
- C: It is not entirely clear cut.
- P: Hmm, that does not sound too good.
- P: So, tell me, are there any risks?
- C: About 50% of patients suffer from minor to moderate pain for 2-3 days afterwards.
- P: That’s a lot!
- P: Anything else?
- C: In some cases, neck manipulation was followed by a stroke.
- P: Gee that’s bad; how often has this happened?
- C: We know of about 500 such cases.
- P: Heavens!
- C: Now, do you want the treatment or not?
- P: How much will you charge?
- C: Only 60 Euros per session.
- P: You mean I have to come back for more, each time risking a stroke?
- C: Well… You don’t have to.
- P: Thanks for the info; I am off. Cherio!
I rest my case.
Reflexology (originally called ‘zone therapy’ by its inventor) is a manual technique where pressure is applied to the sole of the patient’s foot. Reflexology is said to have its roots in ancient cultures. Its current popularity goes back to the US doctor William Fitzgerald (1872-1942) who did some research in the early 1900s and thought to have discovered that the human body is divided into 10 zones each of which is represented on the sole of the foot. Reflexologists thus drew maps of the sole of the foot where all the body’s organs are depicted. Numerous such maps have been published and, embarrassingly, they do not all agree with each other as to the location of our organs on the sole of our feet. By massaging specific zones which are assumed to be connected to specific organs, reflexologists believe to positively influence the function of these organs.
So, does reflexology do more good than harm?
The aim of this review was to conduct a systematic review, meta-analysis, and metaregression to determine the current best available evidence of the efficacy and safety of foot reflexology for adult depression, anxiety, and sleep quality.
Twenty-six studies could be included. The meta-analyses showed that foot reflexology intervention significantly improved adult depression, anxiety, and sleep quality. Metaregression revealed that an increase in total foot reflexology time and duration can significantly improve sleep quality.
The authors concluded that foot reflexology may provide additional nonpharmacotherapy intervention for adults suffering from depression, anxiety, or sleep disturbance. However, high quality and rigorous design RCTs in specific population, along with an increase in participants, and a long-term follow-up are recommended in the future.
Finally a so-called alternative medicine (SCAM) that is backed by soild evidence!
Or perhaps not?
Here are a few concerns that lead me to doubt these conclusions:
- Most of the primary studies were of poor methodological quality.
- Most studies failed to mention adverse effects.
- Very few studies controlled for placebo effects.
- There was evidence of publication bias (negative studies tended to remain unpublished).
- Studies published in languages other than English were not considered.
- The authors fail to point out that a foot massage is, of course, agreeable (and thus may relieve a range of symptoms), but reflexology with all its weird assumptions is less than plausible.
- Many of the studies located by the authors were excluded for reasons that are less than clear.
The last point seems particularly puzzling. Our own trial, for instance, was excluded because, according to the review authors, it did not include relevant outcomes. However, our method secion makes it clear that the primary focus for this study was the subscores for anxiety and depression, which comprise four and seven items, respectively. As it happens, our study was negative.
Also cuirous is the fact that the authors did not mention our own 2011 systematic review of reflexology:
Reflexology is a popular form of complementary and alternative medicine (CAM). The aim of this update is to critically evaluate the evidence for or against the effectiveness of reflexology in patients with any type of medical condition. Six electronic databases were searched to identify all relevant randomised clinical trials (RCTs). Their methodological quality was assessed independently by the two reviewers using the Jadad score. Overall, 23 studies met all inclusion criteria. They related to a wide range of medical conditions. The methodological quality of the RCTs was often poor. Nine high quality RCTs generated negative findings; and five generated positive findings. Eight RCTs suggested that reflexology is effective for the following conditions: diabetes, premenstrual syndrome, cancer patients, multiple sclerosis, symptomatic idiopathic detrusor over-activity and dementia yet important caveats remain. It is concluded that the best clinical evidence does not demonstrate convincingly reflexology to be an effective treatment for any medical condition.
I wonder why!
The aim of this RCT was to examine symptom responses resulting from a home-based reflexology intervention delivered by a friend/family caregiver to women with advanced breast cancer undergoing chemotherapy, targeted, and/or hormonal therapy.
Patient-caregiver dyads (N = 256) were randomized to 4 weekly reflexology sessions or attention control. Caregivers in the intervention group were trained by a reflexology practitioner in a 30-min protocol. During the 4 weeks, both groups completed telephone symptom assessments using the M. D. Anderson Symptom Inventory. Those who completed at least one weekly call were included in this secondary analysis (N = 209). Each symptom was categorized as mild, moderate, or severe using established interference-based cut-points. Symptom response meant an improvement by at least one category or remaining mild. Symptom responses were treated as multiple events within patients and analysed using generalized estimating equations technique.
Reflexology was more successful than attention control in producing responses for pain with no significant differences for other symptoms. In the reflexology group, greater probability of response across all symptoms was associated with lower number of comorbid condition and lower depressive symptomatology at baseline. Compared to odds of responses on pain (chosen as a referent symptom), greater odds of symptom response were found for disturbed sleep and difficulty remembering with older aged participants.
Adjusted odds ratios (ORs) of symptom responses for reflexology arm versus control (adjusted for age, number of comorbid conditions, depressive symptoms at baseline, and treatment type: chemotherapy with or without hormonal therapy versus hormonal therapy alone)
Symptom OR (95% CI) p value
Fatigue 1.76 (0.99, 3.12) 0.06
Pain 1.84 (1.05, 3.23) 0.03
Disturbed sleep 1.45 (0.76, 2.77) 0.26
Shortness of breath 0.58 (0.26, 1.30) 0.19
Remembering 0.96 (0.51, 1.78) 0.89
Lack of appetite 1.05 (0.45, 2.49) 0.91
Dry mouth 1.84 (0.86, 3.94) 0.12
Numbness and tingling 1.40 (0.75, 2.64) 0.29
Depression 1.38 (0.78, 2.43) 0.27
The authors concluded that home-based caregiver-delivered reflexology was helpful in decreasing patient-reported pain. Age, comorbid conditions, and depression are potentially important tailoring factors for future research and can be used to identify patients who may benefit from reflexology.
This is certainly one of the more rigorous studies of reflexology. It is well designed and reported. How valid are its findings? To a large degree, this seems to depend on the somewhat unusual statistical approach the investigators employed:
Baseline characteristics were summarized by study group for outcome values and potential covariates. The unit of analysis was patient symptom; multiple symptoms were treated as nested within the patient being analyzed, using methodology described by Given et al.  and Sikorskii et al. . Patient symptom responses were treated as multiple events, and associations among responses to multiple symptoms within patients were accounted for by specifying the exchangeable correlation structure in the generalized estimating equations (GEE) model. The GEE model was fitted using the GENMOD procedure in SAS 9.4 . A dummy symptom variable with 9 levels was included in the interaction with the trial arm to differentiate potentially different effects of reflexology on different symptoms. Patient-level covariates included age, number of comorbid conditions, type of treatment (chemotherapy or targeted therapy with or without
hormonal therapy versus hormonal therapy only), and the CES-D score at baseline. Odds ratios (ORs) and their 95% confidence intervals (CIs) were obtained for the essential parameter of study group for each symptom.
Another concern is the fact that the study crucially depended on the reliability of the 256 carers. It is conceivable, even likely, I think, that many carers from both groups were less than strict in adhering to the prescribed protocol. This might have distorted the results in either direction.
Finally, the study was unable to control for the possibly substantial placebo response that a reflexology massage unquestionably provokes. Therefore, we are not able to tell whether the observed effect is due to the agreeable, non-specific effects of touch and foot massages, or to the postulated specific effects of reflexology.
This recent Cochrane review assessed the effects of so-called alternative medicine (SCAM) for post-caesarean pain. Randomised clinical trials (RCTs), including quasi-RCTs and cluster-RCTs, comparing SCAM, alone or associated with other forms of pain relief, versus other treatments or placebo or no treatment, for the treatment of post-CS pain were included.
A total of 37 studies (3076 women) investigating 8 different SCAM therapies for post-CS pain relief were found. There was substantial heterogeneity among the trials. The primary outcome measures were pain and adverse effects. Secondary outcome measures included vital signs, rescue analgesic requirement at 6 weeks after discharge; all of which were poorly reported or not reported at all.
The quality of the RCTs was low. Whether acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus placebo plus analgesia) have any effect on pain. Acupuncture or acupressure plus analgesia (versus analgesia) may reduce pain at 12 hours (standardised mean difference (SMD) -0.28, 95% confidence interval (CI) -0.64 to 0.07; 130 women; 2 studies; low-certainty evidence) and 24 hours (SMD -0.63, 95% CI -0.99 to -0.26; 2 studies; 130 women; low-certainty evidence). It is uncertain whether acupuncture or acupressure (versus no treatment) or acupuncture or acupressure plus analgesia (versus analgesia) have any effect on the risk of adverse effects.
Aromatherapy plus analgesia may reduce pain when compared with placebo plus analgesia at 12 hours (mean difference (MD) -2.63 visual analogue scale (VAS), 95% CI -3.48 to -1.77; 3 studies; 360 women; low-certainty evidence) and 24 hours (MD -3.38 VAS, 95% CI -3.85 to -2.91; 1 study; 200 women; low-certainty evidence). The authors were uncertain whether aromatherapy plus analgesia has any effect on adverse effects (anxiety) compared with placebo plus analgesia.
Electromagnetic therapy may reduce pain compared with placebo plus analgesia at 12 hours (MD -8.00, 95% CI -11.65 to -4.35; 1 study; 72 women; low-certainty evidence) and 24 hours (MD -13.00 VAS, 95% CI -17.13 to -8.87; 1 study; 72 women; low-certainty evidence).
There were 6 RCTs (651 women), 5 of which were quasi-RCTs, comparing massage (foot and hand) plus analgesia versus analgesia. All the evidence relating to pain, adverse effects (anxiety), vital signs and rescue analgesic requirement was very low-certainty.
Music therapy plus analgesia may reduce pain when compared with placebo plus analgesia at one hour (SMD -0.84, 95% CI -1.23 to -0.46; participants = 115; studies = 2; I2 = 0%; low-certainty evidence), 24 hours (MD -1.79, 95% CI -2.67 to -0.91; 1 study; 38 women; low-certainty evidence), and also when compared with analgesia at one hour (MD -2.11, 95% CI -3.11 to -1.10; 1 study; 38 women; low-certainty evidence) and at 24 hours (MD -2.69, 95% CI -3.67 to -1.70; 1 study; 38 women; low-certainty evidence). It is uncertain whether music therapy plus analgesia has any effect on adverse effects (anxiety), when compared with placebo plus analgesia because the quality of evidence is very low.
The investigators were uncertain whether Reiki plus analgesia compared with analgesia alone has any effect on pain, adverse effects, vital signs or rescue analgesic requirement because the quality of evidence is very low (one study, 90 women). Relaxation Relaxation may reduce pain compared with standard care at 24 hours (MD -0.53 VAS, 95% CI -1.05 to -0.01; 1 study; 60 women; low-certainty evidence).
Transcutaneous electrical nerve stimulation (TENS)
TENS (versus no treatment) may reduce pain at one hour (MD -2.26, 95% CI -3.35 to -1.17; 1 study; 40 women; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce pain compared with placebo plus analgesia at one hour (SMD -1.10 VAS, 95% CI -1.37 to -0.82; 3 studies; 238 women; low-certainty evidence) and at 24 hours (MD -0.70 VAS, 95% CI -0.87 to -0.53; 108 women; 1 study; low-certainty evidence). TENS plus analgesia (versus placebo plus analgesia) may reduce heart rate (MD -7.00 bpm, 95% CI -7.63 to -6.37; 108 women; 1 study; low-certainty evidence) and respiratory rate (MD -1.10 brpm, 95% CI -1.26 to -0.94; 108 women; 1 study; low-certainty evidence). The authors were uncertain whether TENS plus analgesia (versus analgesia) has any effect on pain at six hours or 24 hours, or vital signs because the quality of evidence is very low (two studies, 92 women).
The authors concluded that some SCAM therapies may help reduce post-CS pain for up to 24 hours. The evidence on adverse events is too uncertain to make any judgements on safety and we have no evidence about the longer-term effects on pain. Since pain control is the most relevant outcome for post-CS women and their clinicians, it is important that future studies of SCAM for post-CS pain measure pain as a primary outcome, preferably as the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. Measuring pain as a dichotomous variable would improve the certainty of evidence and it is easy to understand for non-specialists. Future trials also need to be large enough to detect effects on clinical outcomes; measure other important outcomes as listed in this review, and use validated scales.
I feel that the Cochrane Collaboration does itself no favours by publishing such poor reviews. This one is both poorly conceived and badly reported. In fact, I see little reason to deal with pain after CS differently than with post-operative pain in general. Some of the modalities discussed are not truly SCAM. Most of the secondary endpoints are irrelevant. The inclusion of adverse effects as a primary endpoint seems nonsensical considering that SCAM studies are notoriously bad at reporting them. Many of the allegedly positive findings rely on trial designs that cannot control for placebo effects (e.g A+B versus B); therefore they tell us nothing about the effectiveness of the therapy.
Most importantly, the conclusions are not helpful. I would have simply stated that none of the SCAM modalities are supported by convincing evidence as treatments for pain control after CS.
I have to admit that I had not heard of Dr Bernhoft before. I was alerted to him through the discussions about him on this blog. So, I had a look. What I found amazed me.
On his website, Bernhoft states the following:
Dr. Bernhoft is one of the nation’s leading practitioners in the field of environmental medicine. He comes to his expertise not only through extensive academic and professional training and decades as a practicing physician and surgeon, but also from the uniquely motivating perspective of having been a patient himself who had to fight desperately for his life and was literally forced to find a way to heal himself from an illness that left his MD colleagues at a loss for diagnosis and treatment…
His personal quest for survival carried him into cutting-edge advanced medicine, including gene-environment interactions. He found out that his gene which codes for an enzyme called MTHFR was hypoactive, and a second, which produces GSTM1 was absent, leaving him susceptible to poisoning by a wide range of metals and chemicals…
Because of his unique personal experience, combined with his outstanding professional credentials, he is one of the most effective spokespeople in the cause of environmental healing.
His ‘outstanding professional credentials’ consist of amongst others ‘28 peer reviewed medical articles‘, he claims. My Medline search located just 11:
- Cadmium toxicity and treatment. Bernhoft RA.ScientificWorldJournal. 2013 Jun 3;2013:394652. doi: 10.1155/2013/394652. Print 2013.PMID: 23844395 Free PMC article. Review.
- Mercury toxicity and treatment: a review of the literature.Bernhoft RA.J Environ Public Health. 2012;2012:460508. doi: 10.1155/2012/460508. Epub 2011 Dec 22.PMID: 22235210 Free PMC article. Review.
- Clinical detoxification: elimination of persistent toxicants from the human body.Genuis SJ, Sears ME, Schwalfenberg G, Hope J, Bernhoft R.ScientificWorldJournal. 2013 Jun 6;2013:238347. doi: 10.1155/2013/238347. Print 2013.PMID: 23844383 Free PMC article. No abstract available.
- Incorporating environmental health in clinical medicine.Genuis SJ, Sears M, Schwalfenberg G, Hope J, Bernhoft R.J Environ Public Health. 2012;2012:103041. doi: 10.1155/2012/103041. Epub 2012 May 17.PMID: 22675371 Free PMC article. No abstract available.
- Cholangitis after endoscopic sphincterotomy in patients with stricture of the biliary duct.Kracht M, Thompson JN, Bernhoft RA, Tsang V, Gibson RN, Blumgart LH.Surg Gynecol Obstet. 1986 Oct;163(4):324-6.PMID: 3764637
- Composition and morphologic and clinical features of common duct stones.Bernhoft RA, Pellegrini CA, Motson RW, Way LW.Am J Surg. 1984 Jul;148(1):77-85. doi: 10.1016/0002-9610(84)90292-7.PMID: 6742333
- Pigment sludge and stone formation in the acutely ligated dog gallbladder.Bernhoft RA, Pellegrini CA, Broderick WC, Way LW.Gastroenterology. 1983 Nov;85(5):1166-71.PMID: 6618107
- Vesicular transport of horseradish peroxidase during chronic bile duct obstruction in the rat.Renston RH, Zsigmond G, Bernhoft RA, Burwen SJ, Jones AL.Hepatology. 1983 Sep-Oct;3(5):673-80. doi: 10.1002/hep.1840030508.PMID: 6618434
- Peritoneovenous shunt for refractory ascites: operative complications and long-term results.Bernhoft RA, Pellegrini CA, Way LW.Arch Surg. 1982 May;117(5):631-5. doi: 0.1001/archsurg.1982.01380290081014.PMID: 7073482
- Biliary stricture.Way LW, Bernhoft RA, Thomas MJ.Surg Clin North Am. 1981 Aug;61(4):963-72. doi: 10.1016/s0039-6109(16)42492-8.PMID: 7280936
- The effects of a low level of dietary cadmium on blood pressure, ’24Na, ’42K, andwater retention in growing rats.Doyle JJ, Bernhoft RA, Sandstead HH.J Lab Clin Med. 1975 Jul;86(1):57-63.PMID: 1151143
The following are typical symptoms of hormone imbalance in both men and women:
- Hot flashes and night sweats
- Anxiety, depression, and irritability
- Low libido
- Memory lapses and trouble concentrating
- Weight gain
- Insomnia and sleep apnea
- Lack of muscle tone
Regardless of your age, gender, or specific symptoms, you can find relief with Bioidentical Hormone Replacement Therapy (BHRT).
Women’s Conditions Treated With Bioidentical Hormones
Robin A. Bernhoft, M.D. at the Bernhoft Center for Advanced Medicine specializes in Bioidentical Hormone balancing for women, which includes addressing the symptoms of hormonal imbalance and customizing individual treatment programs using Bioidentical Hormone Replacement Therapy. Robin A. Bernhoft, M.D. will test each woman’s hormone levels to determine deficiencies, dominances, and imbalances, and he will work closely with each woman to find the correct dosages to restore optimal health. Some of the conditions that Doctor Bernhoft uses Bioidentical Hormone Replacement Therapy to treat in women include:
ADRENAL FATIGUE SYNDROME
When you suffer from chronic or poorly managed stress, your adrenal glands do not release the level of cortisol you require to remain healthy and emotionally stable. You may struggle with anxiety, depression, insomnia, fatigue, cravings for sweets, and several other symptoms due to adrenal fatigue. Along with proper nutrition, balancing your hormones with Bioidentical Hormone Replacement Therapy helps you manage stress better by bringing your cortisol levels in balance.
Having too much of the estrogen hormone or an underactive thyroid may cause you to lose hair on your head, arms, legs, or pubic area. If you are diabetic, poor blood sugar control can also cause this problem. Robin A. Bernhoft, M.D. can take a quick blood test to determine if hormonal imbalance is causing this issue. If so, replacing your body’s lost hormones with Bioidentical ones can help you re-grow scalp and body hair.
ANXIETY AND DEPRESSION
When feelings of anxiety and depression are unrelated to a specific life event, they are often the result of unbalanced levels of estrogen, progesterone, and cortisol. You may feel weepy, irritable, nervous, guilty, and many other troublesome emotions. Having a hysterectomy or going through menopause tends to increase your risk of anxiety and depression. When anti-depressant medication doesn’t work, it’s more likely you’re experiencing hormonal depression that is treatable with Bioidentical Hormone Replacement Therapy.
Women who are approaching middle age complain of chronic headaches more often than younger women do. This is often because of pending menopause or being at a certain point in their menstrual cycle. An unbalanced amount of the hormone progesterone may also be the cause of this misery. If Robin A. Bernhoft, M.D. discovers a problem with your progesterone, he may recommend that you start Bioidentical Hormone Replacement Therapy along with a daily dose of the vitamin B12.
CHRONIC FATIGUE SYNDROME
It’s normal to feel tired when you are under stress or don’t get enough sleep, but chronic fatigue lasting throughout the day is probably a sign of hormonal imbalance. Unfortunately, it causes other problems such as irritability, depression, and lowered resistance to illnesses. Low estrogen levels are often the cause of severe fatigue in women. Balancing your hormones with Bioidentical Hormone Replacement Therapy gives you the energy you need to meet everyday responsibilities and enjoy satisfying relationships.
Cystitis, or bladder infections, occurs when bacteria from outside of the body enter through the urinary tract and cause an infection. Hormonal changes that begin in perimenopause may also cause recurring bladder infections. This is because the bladder, urethra, and vagina lose muscle tone and strength as levels of estrogen slowly decline. Fortunately, you can correct this imbalance by receiving Bioidentical Hormone Replacement Therapy. When the muscles near your bladder are stronger, it’s harder for bacteria to invade.
Uterine fibroids are masses of tissue that grow within the wall of your uterus, in it, or on it. It can result in irregular menstrual bleeding or uterine cancer in rare cases. Normally, estrogen stimulates cell growth in your body while progesterone balances it. Fibroids may be the result of unbalanced levels of estrogen, cortisol, xenoestrogens, and progesterone. Bringing all of these necessary hormones in balance with Bioidentical Hormone Replacement Therapy can help to reduce the risk of fibroids.
Insomnia, which is the consistent inability to fall or stay asleep, is both a cause and an effect of hormone imbalance. The hormonal changes of PMS, perimenopause, and menopause can all cause sleeplessness. Chronic insomnia can also make hormone imbalance worse. When your hormones are balanced through Bioidentical Hormone Replacement Therapy, it has a less inhibiting effect on your ability to fall asleep and stay asleep throughout the night.
IRRITABLE BOWEL SYNDROME
IBS is a term that describes pain with bowel movements, urge frequency, a feeling of incomplete bowel emptying, abdominal distension, and several other symptoms. Many women report worsening IBS symptoms just before their period starts. This may occur due to the fluctuation of estrogen and progesterone in the second half of the cycle. Having unbalanced levels of estrogen and progesterone can slow motility in the gut. However, balancing these hormones can greatly alleviate IBS.
LOW SEXUAL LIBIDO
Lack of desire for physical intimacy is due to an imbalance in the amounts of estrogen, progesterone, and testosterone in your body. When the latter two hormones start declining, it may cause estrogen dominance. This problem is also associated with weight gain, mood swings, and painful intercourse, all of which further decrease your libido. Balancing estrogen in your body so it doesn’t dominate other hormones is essential to restore your desire for sex.
Menopause is the clinical term for 12 consecutive months without a menstrual period. As you start menopause, your estrogen, progesterone, and testosterone hormones may fluctuate wildly. Although there are dozens of symptoms associated with menopause, the most common ones include hot flashes, night sweats, low libido, mood swings, and weight gain. Replacement therapy with Bioidentical Hormones can help eliminate or reduce multiple symptoms at the same time.
Although the average age of menopause is 51, you may begin perimenopause as early as your mid 30s. Common symptoms include breast tenderness, changes in the menstrual cycle, skin changes, sexual dysfunction, and loss of bone density. These problems occur due to decreasing levels of estrogen and other essential hormones as you age. If your blood work confirms hormonal imbalance, Bioidentical Hormone Replacement Therapy can help you feel more comfortable.
SYMPTOMS OF PRE-MENSTRUAL SYNDROME
In a normal menstrual cycle, estrogen rises for the first two weeks and then begins to fall. During the second half of the cycle, this process repeats itself with progesterone. If you’re highly sensitive to hormonal changes, you may experience worsening symptoms of PMS. Some of these include bloating, irritability, fatigue, tension, and weight gain. If your PMS symptoms are severe enough to interfere with your quality of life, consider Bioidentical Hormone Replacement Therapy with Doctor Robin A. Bernhoft.
You have a thyroid imbalance when your thyroid, which is a small nodule at the base of your neck, produces too little or too much of this hormone. When you go to a traditional doctor complaining of fatigue or difficulty losing weight, he or she may test your TSH level. However, this may not be enough to determine hormone imbalance. Robin A. Bernhoft, M.D. conducts several medical tests to see if you are a good candidate for Bioidentical Hormone Replacement Therapy.
Men’s Conditions Treated With Bioidentical Hormones
Robin A. Bernhoft, M.D. also specializes in Bioidentical Hormone Replacement Therapy for men, which includes addressing symptoms of hormonal imbalance and customizing individual treatment programs using Bioidentical Hormones. Robin A. Bernhoft, M.D. will apply the newest and most effective methods for restoring optimal hormone balance using Bioidentical Hormone Replacement Therapy. He offers medically supervised programs, which include the most advanced delivery methods to help bring hormone levels back into balance. His programs can also treat the symptoms of andropause, helping men regain their health and confidence. Some of the conditions Robin A. Bernhoft, M.D. uses Bioidentical Hormone Replacement Therapy to treat in men include:
Your adrenal glands release the hormone cortisol in response to stress, exercise, excitement, and low blood sugar. As you age, your body has a harder time balancing your cortisol levels. This can cause unrelenting fatigue, anxiety, sexual problems, and a wide range of other symptoms due to cortisol imbalance in your adrenal glands. Hormone restoration through Bioidentical Hormone Replacement Therapy can help speed up sluggish adrenal glands and provide you with more energy.
ALOPECIA (HAIR LOSS)
Dihydrotestosterone (DHT), which is part of the testosterone hormone, is responsible for hair loss on your scalp, face, chest, back, arms, legs, and groin area. When this hormone is unbalanced, it causes the follicles of your hair to regress and die. High levels of DHT can result in premature balding or thinning hair. If a full head of hair is important to you, remember that Bioidentical Hormone Replacement Therapy can stimulate hair growth.
By the time men reach age 70, they may have only 10 percent of the testosterone hormone they had at age 25. This explains why many men begin experiencing symptoms associated with low testosterone around age 40. Andropause is a term that describes the many physical and emotional changes that occur due to the imbalance of hormones. Testosterone replacement is essential to help you experience long-term symptom relief.
ANXIETY AND DEPRESSION
Low levels of testosterone cause an overall feeling of discontent in some men, which is the hallmark characteristic of hypogonadism. Balanced levels of this hormone are so essential that men with hypogonadism receive a diagnosis of clinical depression 400 times more often than men with normal hormone levels do. If you feel hopeless, low on energy, and irritable, ask Robin A. Bernhoft, M.D. to check your testosterone level. Bioidentical Hormone Replacement Therapy can help balance your hormones and improve your outlook on life.
When fatigue is chronic, you lack the energy to focus or keep up with everyday responsibilities. Declining levels of testosterone are often to blame for this problem. Chronic fatigue is also worsened by other symptoms of andropause, including night sweats, insomnia, sleep apnea, increased stress, and irritability. It’s important to note that all-day fatigue is different than feeling tired. Fortunately, balancing your testosterone and other hormones with Bioidentical Hormone Replacement Therapy helps to improve fatigue and all of its associated symptoms.
Cortisol, the stress hormone, can go into overdrive when you are under constant, unrelenting stress. This can cause daily headaches of varying intensity. The drop in testosterone starting at age 30 can also play a role in chronic headaches; Robin A. Bernhoft, M.D. can pinpoint an exact cause with a simple blood test. If your hormones are unbalanced, treatment with Bioidentical Hormone Replacement Therapy can help alleviate headache pain.
You have erectile dysfunction when you can’t get an erection at all or maintain one long enough for satisfying sexual activity. A diminished level of testosterone is the typical cause. This also happens when the brain fails to signal the release of nitrous oxide, which is responsible for blood flow to the penis. Too much of the stress hormone cortisol also plays a role in erectile dysfunction. Balancing testosterone and cortisol with Bioidentical Hormone Replacement Therapy can eliminate or improve this problem.
Gas, bloating, constipation, diarrhea, heartburn, belching, and slow digestion may all be related to imbalanced hormones in your body. Specifically, these problems could originate due to problems with normal thyroid functioning due to too much cortisol or estrogen. Many traditional doctors don’t treat digestion problems correctly because they don’t understand the connection to hormones. When diet, exercise, and medication aren’t working, consider replacing lost hormones through Bioidentical Hormone Replacement Therapy with Doctor Bernhoft.
Because testosterone normally replenishes itself while you are sleeping, struggling with insomnia lowers your testosterone production. This causes a vicious cycle because low testosterone levels cause many sleep disturbances, including insomnia and sleep apnea. While difficulty falling or staying asleep and decreased testosterone production are both normal signs of aging, you don’t have to allow them to affect your quality of life. Providing your body the testosterone it needs through Bioidentical Hormone Replacement Therapy can greatly improve restful sleep.
IRRITABLE BOWEL SYNDROME
Elevated stress levels and a weakened immune system can both cause IBS, which may present itself as abdominal pain, gas, bloating, or frequent diarrhea. In many cases, both stress and immune system deficiency are related to unbalanced levels of hormones. This can trigger an attack of IBS. Determining what triggers your symptoms, including certain foods and hormone imbalance, is the first step to helping you feel better. Bioidentical Hormone Replacement Therapy helps to balance the hormones responsible for triggering IBS symptoms.
The desire to have sex less often and erectile dysfunction are often related, but it’s possible to have one without the other. Testosterone stimulates the nerves in the brain to become sexually aroused, so this sensation naturally diminishes as you age. Smoking, drinking too much alcohol, and a poor diet are additional reasons your libido may be low. When combined with a healthy lifestyle, therapy with Bioidentical Hormones helps to improve your sexual desire and functioning.
Low testosterone, which your doctor may also refer to as male menopause, hypogonadism, or andropause, is the term used to describe the multitude of symptoms many men experience as they approach middle age. Your testosterone production actually starts declining one percent every year at age 30. Sexual dysfunction, mood problems, weight gain, and low energy are common problems associated with low testosterone that are correctable with Bioidentical Hormone Replacement Therapy.
Low thyroid levels in men can cause cold intolerance, fatigue, hair loss, weight gain, dry skin, and constipation; as many as one in seven men struggle with hypothyroidism. When the thyroid produces an excess of hormones, hyperthyroidism is the result. This condition has many additional symptoms, including muscle weakness, trembling hands, insomnia, and heart palpitations. Having your thyroid level checked by a hormone specialist such as Robin A. Bernhoft, M.D. and completing Bioidentical Hormone Replacement Therapy are essential to help you feel better.
Ojai, California Bioidentical Hormone Replacement Therapy specialist, Robin A. Bernhoft, M.D. at the Bernhoft Center for Advanced Medicine has helped countless men and women to overcome conditions related to hormonal imbalance or decline. Before beginning a Bioidentical Hormone Replacement Therapy program, Robin A. Bernhoft, M.D. tests the levels of all essential hormones in order to get to the root of patients’ imbalances. He then designs a personalized program using dosages that are unique to each patient. Vast numbers of men and women have been able to achieve peak levels of health with Doctor Bernhoft’s specialized Bioidentical Hormone Replacement Therapy programs.
Yes, I did try to find evidence for these claims. It’s a big job and a frustrating one too, as I was less than successful.
Much of so-called alternative medicine (SCAM) is used in the management of osteoarthritis pain. Yet few of us ever seem to ask whether SCAMs are more or less effective and safe than conventional treatments.
This review determined how many patients with chronic osteoarthritis pain respond to various non-surgical treatments. Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counselling, exercise, platelet-rich plasma, viscosupplementation (intra-articular injections usually with hyaluronic acid ), glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids.
In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included:
- exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12),
- intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62),
- SNRIs (RR = 1.53; 95% CI 1.25 to 1.87),
- oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52),
- glucosamine (RR = 1.33; 95% CI 1.02 to 1.74),
- topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38),
- chondroitin (RR = 1.26; 95% CI 1.13 to 1.41),
- viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33),
- opioids (RR = 1.16; 95% CI 1.02 to 1.32).
Pre-planned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analysed, the benefits of opioids were not statistically significant.
The authors concluded that interventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data.
Exercise clearly is an effective intervention for chronic osteoarthritis pain. It has consistently been recommended by international guideline groups as the first-line treatment in osteoarthritis management. The type of exercise is likely not important.
Pharmacotherapies such as NSAIDs and duloxetine demonstrate smaller but statistically significant benefit that continues beyond 12 weeks. Opioids appear to have short-term benefits that attenuate after 4 weeks, and intra-articular steroids after 12 weeks. Limited data (based on 2 RCTs) suggest that acetaminophen is not helpful. These findings are consistent with recent Osteoarthritis Research Society International guideline recommendations that no longer recommend acetaminophen for osteoarthritis pain management and strongly recommend against the use of opioids.
Limited benefit was observed with other interventions including glucosamine, chondroitin, and viscosupplementation. When only publicly funded trials were examined for these interventions, the results were no longer statistically significant.
Adverse events were inconsistently reported. However, withdrawal due to adverse events was consistently reported and found to be greater in patients using opioids, SNRIs, topical NSAIDs, and viscosupplementation.
Few of the interventions assessed fall under the umbrella of so-called alternative medicine (SCAM):
- some forms of exercise,
It is unclear why the authors did not include SCAMs such as chiropractic, osteopathy, massage therapy, acupuncture, herbal medicines, neural therapy, etc. in their review. All of these SCAMs are frequently used for osteoarthritis pain. If they had included these treatments, how do you think they would have fared?
This Cochrane review assessed the efficacy and safety of aromatherapy for people with dementia. The researchers included randomised controlled trials which compared fragrance from plants in an intervention defined as aromatherapy for people with dementia with placebo aromatherapy or with treatment as usual. All doses, frequencies and fragrances of aromatherapy were considered. Participants in the included studies had a diagnosis of dementia of any subtype and severity.
The investigators included 13 studies with 708 participants. All participants had dementia and in the 12 trials which described the setting, all were resident in institutional care facilities. Nine trials recruited participants because they had significant agitation or other behavioural and psychological symptoms in dementia (BPSD) at baseline. The fragrances used were:
- lavender (eight studies);
- lemon balm (four studies);
- lavender and lemon balm,
- lavender and orange,
- cedar extracts (one study each).
For six trials, assessment of risk of bias and extraction of results was hampered by poor reporting. Four of the other seven trials were at low risk of bias in all domains, but all were small (range 18 to 186 participants; median 66). The primary outcomes were:
- overall behavioural,
- psychological symptoms,
- adverse effects.
Ten trials assessed agitation using various scales. Among the 5 trials for which the confidence in the results was moderate or low, 4 trials reported no significant effect on agitation and one trial reported a significant benefit of aromatherapy. The other 5 trials either reported no useable data or the confidence in the results was very low. Eight trials assessed overall BPSD using the Neuropsychiatric Inventory and there was moderate or low confidence in the results of 5 of them. Of these, 4 reported significant benefit from aromatherapy and one reported no significant effect.
Adverse events were poorly reported or not reported at all in most trials. No more than two trials assessed each of our secondary outcomes of quality of life, mood, sleep, activities of daily living, caregiver burden. There was no evidence of benefit on these outcomes. Three trials assessed cognition: one did not report any data and the other two trials reported no significant effect of aromatherapy on cognition. The confidence in the results of these studies was low.
The authors reached the following conclusions: We have not found any convincing evidence that aromatherapy (or exposure to fragrant plant oils) is beneficial for people with dementia although there are many limitations to the data. Conduct or reporting problems in half of the included studies meant that they could not contribute to the conclusions. Results from the other studies were inconsistent. Harms were very poorly reported in the included studies. In order for clear conclusions to be drawn, better design and reporting and consistency of outcome measurement in future trials would be needed.
This is a thorough review. It makes many of the points that I so often make regarding SCAM research:
- too many of the primary studies are badly designed;
- too many of the primary studies are too small;
- too many of the primary studies are poorly reported;
- too many of the primary studies fail to mention adverse effects thus violating research ethics;
- too many of the primary studies are done by pseudo-scientists who use research for promotion rather than testing hypotheses.
It is time that SCAM researchers, ethic review boards, funders, editors and journal reviewers take these points into serious consideration – if only to avoid clinical research getting a bad reputation and losing the support of patients without which it cannot exist.