MD, PhD, MAE, FMedSci, FRSB, FRCP, FRCPEd.

case-control study

Cervical artery dissection (CeAD), which includes both vertebral artery dissection (VAD) and carotid artery dissection (CAD), is the most serious safety concern associated with cervical spinal manipulation (CSM). This study evaluated the association between CSM and CeAD among US adults.“As soon as the chiropractor manipulated my neck, everything went black”

Through analysis of health claims data, the researchers employed a case-control study with matched controls, a case-control design in which controls were diagnosed with ischemic stroke, and a case-crossover design in which recent exposures were compared to exposures in the same case that occurred 6-7 months earlier. The researchers evaluated the association between CeAD and the 3-level exposure, CSM versus office visit for medical evaluation and management (E&M) versus neither, with E&M set as the referent group.

2337 VAD cases and 2916 CAD cases were identified. Compared to population controls, VAD cases were 0.17 (95% CI 0.09 to 0.32) times as likely to have received CSM in the previous week as compared to E&M. In other words, E&M was about 5 times more likely than CSM in the previous week in cases, relative to controls. CSM was 2.53 (95% CI 1.71 to 3.68) times as likely as E&M in the previous week among individuals with VAD than among individuals experiencing a stroke without CeAD. In the case-crossover study, CSM was 0.38 (95% CI 0.15 to 0.91) times as likely as E&M in the week before a VAD, relative to 6 months earlier. In other words, E&M was approximately 3 times more likely than CSM in the previous week in cases, relative to controls. Results for the 14-day and 30-day timeframes were similar to those at one week.

The authors concluded that, among privately insured US adults, the overall risk of CeAD is very low. Prior receipt of CSM was more likely than E&M among VAD patients as compared to stroke patients. However, for CAD patients as compared to stroke patients, as well as for both VAD and CAD patients in comparison with population controls and in case-crossover analysis, prior receipt of E&M was more likely than CSM.

What seems fairly clear from this and a previous similar analysis by the same authors is, I think, this: retrospective studies of this type can unfortunately not provide us with much reliable information about the risks of spinal manipulation. The reasons for this are manyfold, e.g.: less than exact classifications in patients’ records, or the fact that multiple types of spinal manipulations exist of which only some might be dangerous.

Previous research revealed that cognitive abilities are negatively related to right-wing and prejudiced attitudes. No study has, however, investigated if emotional abilities also show such a relationship, although this can be expected based on both classic and recent literature. The aim of the present study was 2-fold:

(a) to investigate the relationship between emotional abilities and right-wing and prejudiced attitudes, and

(b) to pit the effects of emotional and cognitive abilities on these attitudes against each other.

Results from 2 adult samples (n = 409 and 574) in which abilities scores were collected in individual testing sessions, revealed that emotional abilities are significantly and negatively related to social-cultural and economic-hierarchical right-wing attitudes, as well as to blatant ethnic prejudice. These relationships were as strong as those found for cognitive abilities. For economic-hierarchical right-wing attitudes, emotional abilities were even the only significant correlate.

The authors concluded that the study of emotional abilities has the potential to significantly advance our understanding of right-wing and prejudiced attitudes.

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The researchers found that individuals with weaker emotional abilities — particularly emotional understanding and management — tended to score higher on a measure of right-wing authoritarianism and social dominance orientation. Right-wing authoritarianism is a personality trait that describes the tendency to submit to political authority and be hostile towards other groups, while social dominance orientation is a measure of a person’s preference for inequality among social groups.

The results of this study were univocal. People who endorse authority and strong leaders and who do not mind inequality — the two basic dimensions underlying right-wing political ideology — show lower levels of emotional abilities,” said Van Hiel, the lead author of the study. “Those with lower emotional and cognitive abilities were also more likely to agree with blatantly prejudiced statements such as “The White race is superior to all other races.”

Of course, the study only collected correlational data, preventing inferences of causality from being made. “Caution should be exercised in the interpretation of such results,” Van Hiel said. “One cannot discredit any ideology on the basis of such results as those presently obtained. Only in a distant future, we will be able to look back upon our times, and then we can maybe judge which ideologies were the best. Cognitively and emotionally smart people can make wrong decisions as well. The results have been obtained in one particular context. Would similar results be obtained in other contexts besides in a Western country with a long-standing stable democracy? Whether these tendencies are universal, or limited to particular contexts, is very intriguing.”

Semen retention is a so-called alternative medicine (SCAM) that involves intentionally avoiding ejaculating. A person can do this by abstaining from any sexual activity, stopping before the point of ejaculation, or teaching themselves to orgasm without ejaculating.

Although this practice may seem new, this is likely only due to recent internet popularity. In fact, semen retention is an ancient practice, believed to boost male physical and spiritual energy.

Some other names for semen retention include:

  • coitus reservatus
  • seminal conservation
  • sexual continence

It is also known as or included in practices called:

  • karezza (Italian)
  • maithuna (Hindu Tantra)
  • sahaja (Hindu Yoga)
  • tantra (Hinduism and Buddhism)
  • cai Yin pu Yang and cai Yang pu Yin (Taoist)

Semen retention is said to be good for a range of things:

Mental health

  • increased motivation
  • improved energy and focus
  • more self-confidence
  • reduced anxiety
  • better memory
  • improved concentration

Physical health

  • clearer skin
  • increased testosterone
  • more weight loss
  • increased muscle mass
  • physical rejuvenation
  • a deeper voice

Spiritual health

  • a greater sense of purpose
  • stronger or deeper emotional bonds in relationships
  • a stronger sense of overall harmony

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Yes, I agree, this sounds weird!

But is there any evidence?

Yes, e.g.:

Study No 1

Males of some species use mate retention behavior and investment in ejaculate quality as anti-cuckoldry tactics concurrently while others do so in a compensatory fashion. Leivers, Rhodes, and Simmons (2014) reported that men who performed mate retention less frequently produced higher-quality ejaculates, suggesting that humans use these tactics compensatorily. We conducted a conceptual replication of this research in a sample of 41 men (18-33 years; M = 23.33; SD = 3.60). By self-report, participants had not had a vasectomy and had never sought infertility treatment. We controlled for several covariates known to affect ejaculate quality (e.g., abstinence duration before providing an ejaculate) and found no statistically significant relationships between mate retention behavior and four components of ejaculate quality: sperm velocity, sperm concentration, slow motility, and ejaculate volume. The present results provide little support for the hypothesis that human males deploy mate retention behavior and ejaculate quality investment compensatorily. We discuss the limitations of this study and highlight the need for research to address questions about the nature of anti-cuckoldry tactic deployment in humans, especially concerning investment in ejaculate quality.

Study No 2

In species where females mate with multiple males, the sperm from these males must compete to fertilise available ova. Sexual selection from sperm competition is expected to favor opposing adaptations in males that function either in the avoidance of sperm competition (by guarding females from rival males) or in the engagement in sperm competition (by increased expenditure on the ejaculate). The extent to which males may adjust the relative use of these opposing tactics has been relatively neglected. Where males can successfully avoid sperm competition from rivals, one might expect a decrease in their expenditure on tactics for the engagement in sperm competition and vice versa. In this study, we examine the relationship between mate guarding and ejaculate quality using humans as an empirical model. We found that men who performed fewer mate guarding behaviors produced higher quality ejaculates, having a greater concentration of sperm, a higher percentage of motile sperm and sperm that swam faster and less erratically. These effects were found independent of lifestyle factors or factors related to male quality. Our findings suggest that male expenditure on mate guarding and on the ejaculate may represent alternative routes to paternity assurance in humans.

Study No 3

The uncritical application of western psychiatric concepts in non-western societies resulting in culturally invalid psychiatric syndromes, have been extensively documented. Such instances are considered ‘category errors’. In contrast, ‘reverse category errors’ although theoretically postulated, have never been empirically demonstrated. Diagnostic criteria of an established South Asian culture specific neurosis, Dhāt syndrome, were deployed by a psychiatrist of South Asian origin, amongst 47 white Britons in London, UK, presenting for the first time with a clinic diagnosis of ICD-9 Depressive Neurosis (Dysthymic Disroder, ICD-11). The proceedure yielded a new disorder, Semen Retention Syndrome. Based on narrative accounts and quantitative scores on the Hamilton Depression Rating Scale, the evidence suggests that a significant subset of white British subjects diagnosed with Dysthymic Disorder, may in fact be expressing a psychological variation of a previously unknown local White British somatisation phenomena labelled Semen Retention Syndrome. Anxiety and depressive symptoms presented by this subset of subjects were primarily attributed to a core irrational belief and a cognitive error centered around misunderstood concepts of semen physiology. Consequently, the undue focus on mood idioms by both white British patients and their health professionals, leads to a mistaken diagnosis of Mood Disorder, and results in incorrect treatment. The implications of this ethnocentric mode of reasoning raises concerns about existing concepts in psychiatric phenomenology and for official international diagnostic classificatory systems. The paper concludes by arguing that category errors in both directions are instances of cultural iatrogenesis, and underscore the importance of a culturally valid psychiatry.

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I was unable to find support for any of the above-listed effects of semen retention. So, claims like “Semen Retention is life-changing, especially for men. Not only, it help you turn into a real alpha male but also offers great health benefits” need to be taken with a pinch of salt. Yet, it did occur to me that semen retention might have one positive outcome:

It reduces the chances of stupid people multiplying!

 

On this blog, we have some people who continue to promote conspiracy theories about Covid and Covid vaccinations. It is, therefore, time, I feel, to present them with some solid evidence on the subject (even though it means departing from our usual focus on SCAM).

This Cochrane review assessed the efficacy and safety of COVID‐19 vaccines (as a full primary vaccination series or a booster dose) against SARS‐CoV‐2. An impressive team of investigators searched the Cochrane COVID‐19 Study Register and the COVID‐19 L·OVE platform (last search date 5 November 2021). They also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch. They included randomized controlled trials (RCTs) comparing COVID‐19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules.

A total of 41 RCTs could be included and analyzed assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty‐two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty‐nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromised patients. No trials included pregnant women. Sixteen RCTs had two‐month follow-ups or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. The overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. 343 registered RCTs with results not yet available were identified.The evidence for mortality was generally sparse and of low or very low certainty for all WHO‐approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all‐cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high‐certainty evidence).High‐certainty evidence was found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA‐1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP‐CorV (Sinopharm‐Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID‐19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA‐1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP‐CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants).Moderate‐certainty evidence was found that NVX‐CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID‐19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants).There is low‐certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants).High‐certainty evidence was found that BNT162b2, mRNA‐1273, Ad26.COV2.S, and BBV152 result in a large reduction in the incidence of severe or critical disease due to COVID‐19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA‐1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants).

Moderate‐certainty evidence was found that NVX‐CoV2373 probably reduces the incidence of severe or critical COVID‐19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants).

Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled.

mRNA‐1273, ChAdOx1 (Oxford‐AstraZeneca)/SII‐ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in serious adverse events (SAEs) compared to placebo (RR: mRNA‐1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII‐ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants.

Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP‐CorV, and NVX‐CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP‐CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX‐CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants).

The authors’ conclusions were as follows: Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID‐19, and for some, there is high‐certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID‐19 vaccines, and this review is updated regularly on the COVID‐NMA platform (covid-nma.com).

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As some conspiratorial loons will undoubtedly claim that this review is deeply biased; it might be relevant to add the conflicts of interest of its authors:

  • Carolina Graña: none known.
  • Lina Ghosn: none known.
  • Theodoros Evrenoglou: none known.
  • Alexander Jarde: none known.
  • Silvia Minozzi: no relevant interests; Joint Co‐ordinating Editor and Method editor of the Drugs and Alcohol Group.
  • Hanna Bergman: Cochrane Response – consultant; WHO – grant/contract (Cochrane Response was commissioned by the WHO to perform review tasks that contribute to this publication).
  • Brian Buckley: none known.
  • Katrin Probyn: Cochrane Response – consultant; WHO – consultant (Cochrane Response was commissioned to perform review tasks that contribute to this publication).
  • Gemma Villanueva: Cochrane Response – employment (Cochrane Response has been commissioned by WHO to perform parts of this systematic review).
  • Nicholas Henschke: Cochrane Response – consultant; WHO – consultant (Cochrane Response was commissioned by the WHO to perform review tasks that contributed to this publication).
  • Hillary Bonnet: none known.
  • Rouba Assi: none known.
  • Sonia Menon: P95 – consultant.
  • Melanie Marti: no relevant interests; Medical Officer at WHO.
  • Declan Devane: Health Research Board (HRB) – grant/contract; registered nurse and registered midwife but no longer in clinical practice; Editor, Cochrane Pregnancy and Childbirth Group.
  • Patrick Mallon: AstraZeneca – Advisory Board; spoken of vaccine effectiveness to media (print, online, and live); works as a consultant in a hospital that provides vaccinations; employed by St Vincent’s University Hospital.
  • Jean‐Daniel Lelievre: no relevant interests; published numerous interviews in the national press on the subject of COVID vaccination; Head of the Department of Infectious Diseases and Clinical Immunology CHU Henri Mondor APHP, Créteil; WHO (IVRI‐AC): expert Vaccelarate (European project on COVID19 Vaccine): head of WP; involved with COVICOMPARE P et M Studies (APHP, INSERM) (public fundings).
  • Lisa Askie: no relevant interests; Co‐convenor, Cochrane Prospective Meta‐analysis Methods Group.
  • Tamara Kredo: no relevant interests; Medical Officer in an Infectious Diseases Clinic at Tygerberg Hospital, Stellenbosch University.
  • Gabriel Ferrand: none known.
  • Mauricia Davidson: none known.
  • Carolina Riveros: no relevant interests; works as an epidemiologist.
  • David Tovey: no relevant interests; Emeritus Editor in Chief, Feedback Editors for 2 Cochrane review groups.
  • Joerg J Meerpohl: no relevant interests; member of the German Standing Vaccination Committee (STIKO).
  • Giacomo Grasselli: Pfizer – speaking engagement.
  • Gabriel Rada: none known.
  • Asbjørn Hróbjartsson: no relevant interests; Cochrane Methodology Review Group Editor.
  • Philippe Ravaud: no relevant interests; involved with Mariette CORIMUNO‐19 Collaborative 2021, the Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP‐HP Foundation.
  • Anna Chaimani: none known.
  • Isabelle Boutron: no relevant interests; member of Cochrane Editorial Board.

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And as some might say this analysis is not new, here are two further papers just out:

Objectives To determine the association between covid-19 vaccination types and doses with adverse outcomes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the periods of delta (B.1.617.2) and omicron (B.1.1.529) variant predominance.

Design Retrospective cohort.

Setting US Veterans Affairs healthcare system.

Participants Adults (≥18 years) who are affiliated to Veterans Affairs with a first documented SARS-CoV-2 infection during the periods of delta (1 July-30 November 2021) or omicron (1 January-30 June 2022) variant predominance. The combined cohorts had a mean age of 59.4 (standard deviation 16.3) and 87% were male.

Interventions Covid-19 vaccination with mRNA vaccines (BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)) and adenovirus vector vaccine (Ad26.COV2.S (Janssen/Johnson & Johnson)).

Main outcome measures Stay in hospital, intensive care unit admission, use of ventilation, and mortality measured 30 days after a positive test result for SARS-CoV-2.

Results In the delta period, 95 336 patients had infections with 47.6% having at least one vaccine dose, compared with 184 653 patients in the omicron period, with 72.6% vaccinated. After adjustment for patient demographic and clinical characteristics, in the delta period, two doses of the mRNA vaccines were associated with lower odds of hospital admission (adjusted odds ratio 0.41 (95% confidence interval 0.39 to 0.43)), intensive care unit admission (0.33 (0.31 to 0.36)), ventilation (0.27 (0.24 to 0.30)), and death (0.21 (0.19 to 0.23)), compared with no vaccination. In the omicron period, receipt of two mRNA doses were associated with lower odds of hospital admission (0.60 (0.57 to 0.63)), intensive care unit admission (0.57 (0.53 to 0.62)), ventilation (0.59 (0.51 to 0.67)), and death (0.43 (0.39 to 0.48)). Additionally, a third mRNA dose was associated with lower odds of all outcomes compared with two doses: hospital admission (0.65 (0.63 to 0.69)), intensive care unit admission (0.65 (0.59 to 0.70)), ventilation (0.70 (0.61 to 0.80)), and death (0.51 (0.46 to 0.57)). The Ad26.COV2.S vaccination was associated with better outcomes relative to no vaccination, but higher odds of hospital stay and intensive care unit admission than with two mRNA doses. BNT162b2 was generally associated with worse outcomes than mRNA-1273 (adjusted odds ratios between 0.97 and 1.42).

Conclusions In veterans with recent healthcare use and high occurrence of multimorbidity, vaccination was robustly associated with lower odds of 30 day morbidity and mortality compared with no vaccination among patients infected with covid-19. The vaccination type and number of doses had a significant association with outcomes.

SECOND EXAMPLE Long COVID, or complications arising from COVID-19 weeks after infection, has become a central concern for public health experts. The United States National Institutes of Health founded the RECOVER initiative to better understand long COVID. We used electronic health records available through the National COVID Cohort Collaborative to characterize the association between SARS-CoV-2 vaccination and long COVID diagnosis. Among patients with a COVID-19 infection between August 1, 2021 and January 31, 2022, we defined two cohorts using distinct definitions of long COVID—a clinical diagnosis (n = 47,404) or a previously described computational phenotype (n = 198,514)—to compare unvaccinated individuals to those with a complete vaccine series prior to infection. Evidence of long COVID was monitored through June or July of 2022, depending on patients’ data availability. We found that vaccination was consistently associated with lower odds and rates of long COVID clinical diagnosis and high-confidence computationally derived diagnosis after adjusting for sex, demographics, and medical history.

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There are, of course, many more articles on the subject for anyone keen to see the evidence. Sadly, I have little hope that the COVID loons will be convinced by any of them. Yet, I thought I should give it nevertheless a try.

A team of French researchers assessed whether a conflict of interest (COI) might be associated with the direction of the results of meta-analyses of homoeopathy trials. Their analysis (published as a ‘letter to the editor) is complex, therefore, I present here only their main finding.

The team conducted a literature search until July 2022 on PubMed and Embase to identify meta-analyses of randomized clinical trials assessing the efficacy of homoeopathy. They then assessed the existence of potential COI, defined by the presence of at least one of the following criteria:

  • affiliation of one or more authors to an academic homoeopathy research or care facility, or to the homoeopathy industry;
  • research sponsored or funded by the homoeopathy industry;
  • COI declared by the authors.

The researchers also evaluated and classified any spin in meta-analyses conclusions into three categories (misleading reporting, misleading interpretation and inappropriate extrapolation). Two reviewers assessed the quality of meta-analyses and the risk of bias based. Publication bias was evaluated by the funnel plot method. For all the studies included in these meta-analyses, the researchers checked whether they reported a statistically significant result in favour of homoeopathy. Further details about the methods are provided on OSF (https://osf.io/nqw7r/) and in the preregistered protocol (CRD42020206242).

Twenty meta-analyses were included in the analysis (list of references available at https://osf.io/nqw7r/).

  • Among the 13 meta-analyses with COI, a significantly positive effect of homoeopathy emerged (OR=0.60 (95% CI 0.50 to 0.70)).
  • There was no such effect for meta-analyses without COI (OR=0.96 (95% CI 0.75 to 1.23)).

The authors concluded that in the presence of COI, meta-analyses of homoeopathy trials are more likely
to have favourable results. This is consistent with recent research suggesting that systematic reviews with financial COI are associated with more positive outcomes.

Meta-analyses are systematic reviews (critical assessments of the totality of the available evidence) where the data from the included studies are pooled. For a range of reasons, this may not always be possible. Therefore the number of meta-analyses (20) is substantially lower than that of the existing systematic reviews (>50).

Both systematic reviews and meta-analyses are theoretically the most reliable evidence regarding the value of any intervention. I said ‘theoretically’ because, like any human endeavour, they need to be done in an unbiased fashion to produce reliable results. People with a conflict of interest by definition struggle to be free of bias. As we have seen many times, this would include homoeopaths.

This new analysis confirms what many of us have feared. If proponents of homeopathy with an overt conflict of interest conduct a meta-analysis of studies of homeopathy, the results tend to be more positive than when independent researchers do it. The question that emerges from this is the following:

Are the findings of those researchers who have an interest in producing a positive result closer to the truth than the findings of researchers who have no such conflict?

I let you decide.

The well-known Dr. Chris van Tulleken recently joined forces with Professor Michael Heinrich and Dr. Anthony Booker from the University College London School of Pharmacy to test a range of herbal products on sale in the UK. They bought over 70 herbal products from various high street stores and internet retailers. Some of the products were ‘THR’ (traditional herbal registration) herbal medicines, and some were marketed as food supplements. They then analyzed their chemistry to see whether each one really contained what the label says. The three popular herbal remedies we tested were:-

  • Milk thistle (Silybum marianum),
  • Ginkgo (Ginkgo biloba),
  • Evening primrose (Oenothera).

The team at UCL used two different methods of analysis to verify the identity of these herbal products and extracts. High-performance thin-layer chromatography (HPTLC) is a sophisticated technique for the analysis of herbal products and is one of the most commonly used methods in the industry. HPTLC analysis creates a chemical fingerprint of the product which the researchers can then compare to an accepted reference standard for the herb. They look for a broad spectrum of ‘marker compounds’ these are the pharmacologically active and/or chemical constituents within a plant that can be used to verify its potency or identity. For complex samples or where additional confirmation is required, researchers often turn to ¹H nuclear magnetic resonance spectroscopy (¹H-NMR) which allows individual samples to be compared in detail against other samples or to the whole group.

In every THR product tested, the product contained what was claimed on the label. However, the food supplements showed a wide range of quality.

  • Of the food supplement products labeled as Ginkgo, 8 out of 30 (27%) contained little or no ginkgo extract.
  • 36% of the food supplement milk thistle products contained no detectable milk thistle. Although this is quite a small sample size it is still a startling result. Furthermore, in one case of milk thistle, unidentified adulterants suspected to be synthetic compounds were present in place of milk thistle.
  • All of the evening primrose food products we tested did contain what the packet claimed.

The researchers concluded that their investigation shows that a regulatory system for herbal products, like the THR scheme, ensures that people have access to safe herbal medicine products. So, if you are considering buying herbal products then do look out for the THR mark– otherwise, you might not just be wasting your money, you might be consuming other, potentially dangerous, ingredients.

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This is an interesting investigation. The researchers should be commended for it! However, I disagree with some of their conclusions. Here is why:

  • The investigation merely tested the quality of the products and NOT THEIR SAFETY! To claim that the THR ensures access to safe herbal medicines is incorrect. A product might be of adequate quality but can still be unsafe. The THR only implies safety because the herbal has been used for years without problems being noted. This is not the same as ensuring that it is safe. A direct test of safety is usually not available.
  • The recommendation to buy a product with a THR mark is also somewhat misleading. It implies that these products are effective. I fail to see convincing evidence that either MILK THISTLE, GINKGO, or EVENING PRIMROSE  are effective for any disease or condition. Thus the responsible recommendation should, in my view, be to NOT buy them regardless of whether they are of good quality or not.

 

 

Imagine you have caught a cold. You think it is not necessary to see a doctor, but you want to take something that helps your body to get better. What is your choice of remedy? There are many options provided by conventional medicine as well as by so-called alternative medicine (SCAM).

Many people opt for SCAM to address health issues or prevent diseases. Yet, the evidence for SCAMs is either lacking or controversial due to methodological weaknesses. Thus, practitioners and patients primarily rely on subjective references rather than credible evidence from systematic research.

This study investigated whether cognitive and personality factors explain the differences in belief in SCAM and homeopathy. The researchers investigated the robustness of 21 predictors when examined together to obtain insights into some key determinants of such beliefs in a sample of 599 participants (60% female, 18-81 years). A combination of predictors explained 20% of the variance in SCAM belief. These predictors were:

  • ontological confusions,
  • spiritual epistemology,
  • agreeableness,
  • death anxiety,
  • gender.

Approximately 21% of the variance in belief in homeopathy was explained by the following predictors:

  • ontological confusions,
  • illusory pattern perception,
  • need for cognitive closure,
  • need for cognition,
  • honesty-humility,
  • death anxiety,
  • gender,
  • age.

The authors concluded that some of the predictors from previous research replicated whereas others did not. Demographics and certain cognitive variables seem to be key determinants associated with beliefs in SCAM and homeopathy. Those individual differences and cognitive biases might result in a different perception of the world. However, variables related to abilities did not predict the beliefs. Thus, they might not be a result of inability but rather of ignorance.

Previous studies have shown that SCAM believers tend to believe in paranormal phenomena and conspiracies. I think that, in the discussion sections of this blog, we have ample evidence for this to be true. Paranormal beliefs are usually built on a magical worldview without reasoned review, which is shared by SCAM proponents. Such beliefs advocate emotional criteria for truth instead of data and logical considerations. Another belief, namely spirituality, is closely related to paranormal beliefs and religiosity and also associated with being a SCAM user. Lindeman found that SCAM belief could be best explained by intuitive reasoning, paranormal beliefs, and ontological confusions, defined as category mistakes in which properties of living and lifeless entities are mixed.

The authors point out that their results do not replicate previous findings that showed predictive value of certain cognitive variables such as cognitive style. An explanation could be that rather inattention to accuracy than the inability to consider empirical evidence fosters the beliefs. People might simply not be aware of the absence of evidence. Another possibility is that people are aware of the absence of evidence but are reluctant to engage with it. Practitioners and patients often claim “whatever works is good” or “the main thing is that it works”. Thus, it is ignorance rather than a lack of capacity to appropriately process the evidence.

The authors of this study are well aware of the limitations of their research:

“As with most cross-sectional studies using questionnaires, our results are based on self-reports. Additionally, single items were used for measuring belief strength. Even if multi-item measures often have advantages, single items can be advantageous in terms of practical benefits, e.g., adapting to subjects’ limited attention and time resources. There are several single item measures successfully used to measure diverse concepts including attitudes. Also, the variance on those items in our sample shows that participants were able to reflect their beliefs and rank them on the scale provided. Another limitation is that the findings are based on regression analyses, which do not provide insight into causality. Thus, the relationship remains correlational. Even if our sample was broader than in many other psychological studies—it was slightly unbalanced, especially in comparison to the German population. It over-represented educated individuals which may lead to an inadequate variation of the cognitive variables if we consider the relationship between cognition and education. However, education and the cognitive variables are only weakly correlated. Thus, it can be assumed that the unbalanced sample did not affect the distribution of cognitive variables to a great extent.”

The ‘keto diet’ is a currently popular high-fat, low-carbohydrate diet; it limits the intake of glucose which results in the production of ketones by the liver and their uptake as an alternative energy source by the brain. It is said to be an effective treatment for intractable epilepsy. In addition, it is being promoted as a so-called alternative medicine (SCAM) for a wide range of conditions, including:

  • weight loss,
  • cognitive and memory enhancement,
  • type II diabetes,
  • cancer,
  • neurological and psychiatric disorders.

Now, it has been reported that the ‘keto diet’ may be linked to higher levels of cholesterol and double the risk of cardiovascular events. In the study, researchers defined a low-carb, high-fat (LCHF) diet as 45% of total daily calories coming from fat and 25% coming from carbohydrates. The study, which has so far not been peer-reviewed, was presented Sunday at the American College of Cardiology’s Annual Scientific Session Together With the World Congress of Cardiology.

“Our study rationale came from the fact that we would see patients in our cardiovascular prevention clinic with severe hypercholesterolemia following this diet,” said Dr. Iulia Iatan from the Healthy Heart Program Prevention Clinic, St. Paul’s Hospital, and University of British Columbia’s Centre for Heart Lung Innovation in Vancouver, Canada, during a presentation at the session. “This led us to wonder about the relationship between these low-carb, high-fat diets, lipid levels, and cardiovascular disease. And so, despite this, there’s limited data on this relationship.”

The researchers compared the diets of 305 people eating an LCHF diet with about 1,200 people eating a standard diet, using health information from the United Kingdom database UK Biobank, which followed people for at least a decade. They found that people on the LCHF diet had higher levels of low-density lipoprotein and apolipoprotein B. Apolipoprotein B is a protein that coats LDL cholesterol proteins and can predict heart disease better than elevated levels of LDL cholesterol can. The researchers also noticed that the LCHF diet participants’ total fat intake was higher in saturated fat and had double the consumption of animal sources (33%) compared to those in the control group (16%). “After an average of 11.8 years of follow-up – and after adjustment for other risk factors for heart disease, such as diabetes, high blood pressure, obesity, and smoking – people on an LCHF diet had more than two times higher risk of having several major cardiovascular events, such as blockages in the arteries that needed to be opened with stenting procedures, heart attack, stroke, and peripheral arterial disease.” Their press release also cautioned that their study “can only show an association between the diet and an increased risk for major cardiac events, not a causal relationship,” because it was an observational study, but their findings are worth further investigation, “especially when approximately 1 in 5 Americans report being on a low-carb, keto-like or full keto diet.”

I have to say that I find these findings not in the slightest bit surprising and would fully expect the relationship to be causal. The current craze for this diet is concerning and we need to warn consumers that they might be doing themselves considerable harm.

Other authors have recently pointed out that, within the first 6-12 months of initiating the keto diet, transient decreases in blood pressure, triglycerides, and glycosylated hemoglobin, as well as increases in HDL and weight loss may be observed. However, the aforementioned effects are generally not seen after 12 months of therapy. Despite the diet’s favorable effect on HDL-C, the concomitant increases in LDL-C and very-low-density lipoproteins (VLDL) may lead to increased cardiovascular risks. And another team of researchers has warned that “given often-temporary improvements, unfavorable effects on dietary intake, and inadequate data demonstrating long-term safety, for most individuals, the risks of ketogenic diets may outweigh the benefits.”

In this retrospective matched-cohort study, Chinese researchers investigated the association of acupuncture treatment for insomnia with the risk of dementia. They collected data from the National Health Insurance Research Database (NHIRD) of Taiwan to analyze the incidence of dementia in patients with insomnia who received acupuncture treatment.

The study included 152,585 patients, selected from the NHIRD, who were newly diagnosed with insomnia between 2000 and 2010. The follow-up period ranged from the index date to the date of dementia diagnosis, date of withdrawal from the insurance program, or December 31, 2013. A 1:1 propensity score method was used to match an equal number of patients (N = 18,782) in the acupuncture and non-acupuncture cohorts. The researchers employed Cox proportional hazards models to evaluate the risk of dementia. The cumulative incidence of dementia in both cohorts was estimated using the Kaplan–Meier method, and the difference between them was assessed through a log-rank test.

Patients with insomnia who received acupuncture treatment were observed to have a lower risk of dementia (adjusted hazard ratio = 0.54, 95% confidence interval = 0.50–0.60) than those who did not undergo acupuncture treatment. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (log-rank test, p < 0.001).

The researchers concluded that acupuncture treatment significantly reduced or slowed the development of dementia in patients with insomnia.

They could be correct, of course. But, then again, they might not be. Nobody can tell!

As many who are reading these lines know: CORRELATION IS NOT CAUSATION.

But if acupuncture was not the cause for the observed differences, what could it be? After all, the authors used clever statistics to make sure the two groups were comparable!

The problem here is, of course, that they can only make the groups comparable for variables that were measured. These were about 20 parameters mostly related to medication intake and concomitant diseases. This leaves a few hundred potentially relevant variables that were not quantified and could thus not be accounted for.

My bet would be lifestyle: it is conceivable that the acupuncture group had acupuncture because they were generally more health-conscious. Living a relatively healthy life might reduce the dementia risk entirely unrelated to acupuncture. According to Occam’s razor, this explanation is miles more likely that the one about acupuncture.

So, what this study really demonstrates or implies is, I think, this:

  1. The propensity score method can never be perfect in generating completely comparable groups.
  2. The JTCM publishes rubbish.
  3. Correlation is not causation.
  4. To establish causation in clinical medicine, RCTs are usually the best option.
  5. Occam’s razor can be useful when interpreting research findings.

This prospective study aimed to identify an optimal lifestyle profile to protect against memory loss in older individuals from areas representative of the north, south, and west of China. Individuals aged 60 years or older who had normal cognition and underwent apolipoprotein E (APOE) genotyping at baseline in 2009 were included. Participants were followed up until death, discontinuation, or 26 December 2019.

Six lifestyle factors were assessed:

  • a healthy diet (adherence to the recommended intake of at least 7 of 12 eligible food items),
  • regular physical exercise (≥150 min of moderate intensity or ≥75 min of vigorous intensity, per week),
  • active social contact (≥twice per week),
  • active cognitive activity (≥twice per week),
  • never or previously smoked,
  • never drinking alcohol.

Participants were categorised into the favourable group if they had 4-6 healthy lifestyle factors, into the average group for two to three factors, and into the unfavourable group for zero to one factor.

Memory function was assessed using the World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test, and global cognition was assessed via the Mini-Mental State Examination. Linear mixed models were used to explore the impact of lifestyle factors on memory in the study sample.

A total of 29 072 participants were included (mean age of 72.23 years; 48.54% (n=14 113) were women; and 20.43% (n=5939) were APOE ε4 carriers). Over the 10-year follow-up period (2009-19), participants in the favourable group had slower memory decline than those in the unfavourable group (by 0.028 points/year, 95% confidence interval 0.023 to 0.032, P<0.001). APOE ε4 carriers with favourable (0.027, 95% confidence interval 0.023 to 0.031) and average (0.014, 0.010 to 0.019) lifestyles exhibited a slower memory decline than those with unfavourable lifestyles. Among people who were not carriers of APOE ε4, similar results were observed among participants in the favourable (0.029 points/year, 95% confidence interval 0.019 to 0.039) and average (0.019, 0.011 to 0.027) groups compared with those in the unfavourable group. APOE ε4 status and lifestyle profiles did not show a significant interaction effect on memory decline (P=0.52).

The authors concluded that a healthy lifestyle is associated with slower memory decline, even in the presence of the APOE ε4 allele. This study might offer important information to protect older adults against memory decline.

This is an important and meticulously reported study. It is the first large-scale investigation that assesses the effects of different lifestyle profiles, APOE ε4 status, and their interactions on longitudinal memory trajectories over a 10-year follow-up period. The results show that lifestyle is associated with the rate of memory decline in cognitively normal older individuals, including in people who are genetically susceptible to memory decline. The authors are rightly careful to avoid causal inferences between lifestyle and memory decline. To demonstrate causality beyond doubt, we would need different study designs.

The authors also discuss several weaknesses of the study:

  • Firstly, the assessments of lifestyle factors were based on self-reports and are, therefore, prone to measurement errors.
  • Secondly, several participants were excluded due to missing data or not returning for follow-up evaluations, which might have led to selection bias.
  • Thirdly, the proportion of individuals with an unhealthy lifestyle might have been underestimated in the study because people with poor health were less likely to have participated in the study.
  • Fourthly, given the nature of the study design, it could not assess whether maintaining a healthy lifestyle had already started influencing memory by the time of enrolment in the study.
  • Fifthly, the evaluation of memory using a single neuropsychological test that does not comprehensively reflect overall memory function. However, the Auditory Verbal Learning Test is an effective instrument for memory assessment, and a composite score was used based on four Auditory Verbal Learning Test subscales to represent memory conditions to the greatest extent possible.
  • Sixthly, as participants might become familiar with repeated cognitive testing, a learning effect could have influenced the results.
  • Finally, memory decline was studied solely among older adults; however, memory problems commonly affect young individuals as well.

The authors, therefore, state that further studies should be conducted to facilitate a more extensive investigation into the effects of a healthy lifestyle on memory decline across the lifespan. This approach would help to elucidate the crucial age window during which a healthy lifestyle can exert the most favourable effect.

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