Pro-inflammatory cytokines serve an important purpose, in marshaling the inflammatory response that fights off viruses, bacteria, and other pathogens. That’s the protective mechanism of inflammation at work. But for the pro-inflammatory cytokine response to be beneficial, it must be proportional to the threat. A too vigorous response of pro-inflammatory cytokines creates a dangerous amount of inflammation—and can actually serve to spread the viral infection, rather than tamping it down. It is this inflammatory overreaction and viral spread that appears to take place in the most serious cases of COVID-19.
I spent 10 minutes on the Internet trying to find the appropriate dose of melatonin for its possible preventative and treatment powers. But no luck. It’s likely in the range of 1 to 10 mg/day, typically taken at night or bedtime. For insomnia in my hospitalized patients, I start at 1.5 mg. Most of my colleagues use a much higher dose. Dr Josh Farkas at emcrit.org suggests that the treatment dose is 5 mg/day.
As always, check with your personal physician first.
If you’re looking for evidence that stay-at-home orders and business closures don’t help control COVID-19, here it is:
In summary, we fail to find strong evidence supporting a role for more restrictive non-pharmacological interventions in the control of COVID in early 2020. We do not question the role of all public health interventions, or of coordinated communications about the epidemic, but we fail to find an additional benefit of stay-at-home orders and business closures.
The title above sums it up. If you’re eating pasta frequently and trying to lose weight, you do have to be careful not to over-eat. In other words, you generally have to restrict calories. In the study at hand, I don’t know how many daily calories were allowed since I haven’t read the full report. Here’s the abstract:
Background & aims
The effect of pasta consumption within a low-energy [read: calorie-restricted] Mediterranean diet on body weight regulation has been scarcely explored. This paper investigates the effect of two Mediterranean diets, which differed for lower or higher pasta intake, on body weight change in individuals with obesity.
Methods & Results
Forty-nine volunteers finished a quasi-experimental 6-month two–parallel group dietary intervention. Participants were assigned to a low-energy high pasta (HP) or to a low-energy low Pasta (LP) group on the basis of their pasta intake (HP ≥ 5 or LP ≤ 3 times/week). Anthropometrics, blood pressure and heart rate were measured every month. Weight maintenance was checked at month 12. Body composition (bioelectrical impedance analysis, BIA), food intake (24-h recall plus a 7-day carbohydrate record) and the perceived quality of life (36-item short-form health survey, SF-36) were assessed at baseline, 3 and 6 months. Blood samples were collected at baseline and month 6 to assess glucose and lipid metabolism. After 6-month intervention, body weight reduction was −10 ± 8% and −7 ± 4% in HP and LP diet, respectively, and it remained similar at month 12. Both dietary interventions improved anthropometric parameters, body composition, glucose and lipid metabolism, but no significant differences were observed between treatment groups. No differences were observed for blood pressure and heart rate between treatments and among times. HP diet significantly improved perception of quality of life for the physical component.
Independent of pasta consumption frequency, low-energy Mediterranean diets were successful in improving anthropometrics, physiological parameters and dietary habits after a 6-month weight-loss intervention.
I often get pages from hospital nurses regarding a patient’s request for a sleeping pill. (Or is the request really from the nurse because a sleeping patient is less hassle? LOL.) My hospital’s formulary limits me to ambien, restoril, trazodone, benadryl, and melatonin. Of those, melatonin seems to be the safest. But does it work?
The evidence is mixed and weak. There is some positive evidence for melatonin, and side effects are mild. I wouldn’t discourage anyone who wants to give it a try, but I think good sleep hygiene measures would be a better first step for treating insomnia.
The optimum dosage has not been established. In studies, the doses have ranged from 1 to 12 mg. Supplements typically contain 1-3 mg. Dosages between 1 and 10 mg can raise melatonin levels to 3-60 times the levels normally found in the body.
Caution is advisable, since quality control is a documented problem. 71% of products did not contain within 10% of the labelled amount of melatonin, with variations ranging from -83% to +478%, lot-to-lot variability was as high as 465%, and the discrepancies were not correlated to any manufacturer or product type. To make matters worse, 8 out of 31 products were contaminated with the neurotransmitter serotonin.
If melatonin works by placebo effect alone, it will help ~10% of users, almost always without adverse effects. I dose it at 1.5 mg, with a repeat dose an hour later if needed.
<p class="has-drop-cap" value="<amp-fit-text layout="fixed-height" min-font-size="6" max-font-size="72" height="80"><span class="has-inline-color has-black-color">The Swiss have the U.S. beat in terms of longevity and percentage of gross domestic product devoted to healthcare. Their healthcare system may or may not have something to do with it.</span> Switzerland, which has twice as many square miles as New Jersy, only has 8,700,000 people compared to the 331,000,000 in the U.S. The Swiss have the U.S. beat in terms of longevity and percentage of gross domestic product devoted to healthcare. Their healthcare system may or may not have something to do with it. Switzerland, which has twice as many square miles as New Jersy, only has 8,700,000 people compared to the 331,000,000 in the U.S.
This analysis of the Swiss health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. The Swiss health system is highly complex, combining aspects of managed competition and corporatism (the integration of interest groups in the policy process) in a decentralized regulatory framework shaped by the influences of direct democracy. The health system performs very well with regard to a broad range of indicators. Life expectancy in Switzerland (82.8 years) is the highest in Europe after Iceland, and healthy life expectancy is several years above the European Union (EU) average. Coverage is ensured through mandatory health insurance (MHI), with subsidies for people on low incomes. The system offers a high degree of choice and direct access to all levels of care with virtually no waiting times, though managed care type insurance plans that include gatekeeping restrictions are becoming increasingly important. Public satisfaction with the system is high and quality is generally viewed to be good or very good. Reforms since the year 2000 have improved the MHI system, changed the financing of hospitals, strengthened regulations in the area of pharmaceuticals and the control of epidemics, and harmonized regulation of human resources across the country. In addition, there has been a slow (and not always linear) process towards more centralization of national health policy-making. Nevertheless, a number of challenges remain. The costs of the health care system are well above the EU average, in particular in absolute terms but also as a percentage of gross domestic product (GDP) (11.5%). MHI premiums have increased more quickly than incomes since 2003. By European standards, the share of out-of-pocket payments is exceptionally high at 26% of total health expenditure (compared to the EU average of 16%). Low and middle-income households contribute a greater share of their income to the financing of the health system than higher-income households. Flawed financial incentives exist at different levels of the health system, potentially distorting the allocation of resources to different providers. Furthermore, the system remains highly fragmented as regards both organization and planning as well as health care provision.
I wonder if we should adopt some of their system’s attributes.
Remdesivir and hydroxychloroquine don’t do much good for hospitalized COVID-19 patients, according to this abstract of the SOLIDARITY trial:
World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19).
We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.
At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.
These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay.
The morbidity and mortality impact on public health from SARS-CoV-2 must be balanced with the risks and costs of a vaccine roll-out. We have shown that the mortality and morbidity from SARS-CoV-2 is no longer an existential threat to society.
It is a huge responsibility to roll out a vaccine manufactured with novel technology. To do so with the intention that all 60+ million people in the UK should receive the vaccine as soon as possible, without full transparency as to potential risks, may be viewed as irresponsible, potentially even negligent, from a legal standpoint. We urge you to heed the wisdom in the Hippocratic Oath: “First, do no harm“.
The only alliance team member I’ve heard of is Dr Malcolm Kendrick. I’m sure none of them have ever heard of me.
I haven’t decided what I’ll tell my my mother if she asks me if she should take the vaccine soon. She’s 89 years old and readily admits she’s ready to go to Heaven. What has she got to lose? I’ll back her choice either way.
The Justice Department alleges Walmart violated federal law by selling thousands of prescriptions for controlled substances that its pharmacists “knew were invalid,” said Jeffrey Clark, the acting assistant attorney general in charge of the Justice Department’s civil division.
Federal law required Walmart to spot suspicious orders for controlled substances and report those to the Drug Enforcement Administration, but prosecutors charge the company didn’t do that.
This could get interesting. Questions immediately arise:
Are the Feds trying to deflect blame from themselves?
Did Walmart fail to make adequate political contributions and/or bribes?
Pharmacists, not pharmacies, are supposed to be on the lookout for illegitimate prescriptions. Where do they stand in this?
Will the customers or “patients” be let off the hook?
Is this just a bold career move by a stagnant Justice Department bureaucrat?
Are the Feds trying to extort Walmart to help reduce the federal deficit?
I haven’t read the entire article below and probably won’t ever. It will be used to promote treatment of mild to moderate hypertension in order to prevent dementia, despite cost and drug side effects. Results are distinctly unimpressive. Four years of drug therapy reduced the incidence of dementia and cognitive decline by less than 1%.
I was expecting and hoping for a much more significant reduction. Nevertheless, anti-hypertensive drug therapy is pretty well established as an effective preventative for cardiovascular disease, including stroke.
From JAMA Network:
Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I2 = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I2 = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores.
Conclusions and Relevance
In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.
I’ve run across a number of people who slowly increased their alcohol consumption over months or years, not realizing it was causing or would cause problems for them. Alcohol is dangerous, lethal at times.
From a health standpoint, the generally accepted safe levels of consumption are:
no more than one standard drink per day for women
no more than two standard drinks per day for men
One drink is 5 ounces of wine, 12 ounces of beer, or 1.5 ounces of 80 proof distilled spirits (e.g., vodka, whiskey, gin).
Dry January was conceived in the UK in 2012 or 2014. The idea is simply to abstain from all alcohol for the month of January. The Alcohol Change UK website can help you git ‘er done. Many folks notice that they sleep better, have more energy, lose weight, and save money. There are other potential benefits.
If you think you may have an unhealthy relationship with alcohol, check your CAGE score. It’s quick and easy.
Alternatively, if you make a commitment to a Dry January but can’t do it, you may well have a problem.
PS: I did the Dry January in January 2020. The only definite change I saw was that I was more productive. E.g., I blogged more regularly, worked out a bit more. The lesson for me is that alcohol makes me a little lazy. At three weeks in, I started thinking maybe I was able to fall asleep sooner but still woke up often, as usual. I also lost three pounds of body weight fat, but had consciously cut back on food intake.