Hengartner et al. conducted a meta-analysis on suicide risk with selective serotonin reuptake inhibitors (SSRI) and other new-generation antidepressants in adults (1). Although the pooled relative risks (RRs) of SSRI for suicide risk including suicide and suicide attempt in patients with depression and in patients with all indications did not reach the level of significance, the pooled RR (95% confidence intervals [CIs]) of any new-generation antidepressant for suicide risk in patients with depression and in patients with all indications were 1.29 (1.06-1.57) and 1.45 (1.23-1.70), respectively. The authors presented information on the different suicide risk between SSRI and other new-generation antidepressants , and I present additional information regarding the relationship.

First, Sharma et al. conducted a meta-analysis on the association of SSRI and serotonin-norepinephrine reuptake inhibitors with suicidality and other mental indicators (2). Although the pooled odds ratios (ORs) of antidepressant treatment for suicidality and aggression did not reach the level of significance in adults, the pooed ORs (95% CIs) of antidepressant treatment for suicidality and aggression were 2.39 (1.31-4.33) and 2.79 (1.62-4.81) in children/adolescents. The suicide risk differed in different generations, and suicide risk estimation should be conducted by stratification with generation and type of anti-depressants.

Second, Hengartner and Plöderl reported that odds ratios (ORs) (95% confidence intervals [CIs]) of antidepressant treatment for suicides and suicide attempts were 2.83 (1.13-9.67) and 2.38 (1.63-3.61), respectively (3). By using the same database, Kaminski et al. reported that ORs (95% CIs) of antidepressant treatment for suicides and suicide attempts were 1.98 (0.71-5.50) and 1.63 (1.09-2.43), respectively (4). In case of rare events, the level of significance in OR differed by applying different analytical approaches. This means that marginal level of significance should be verified by further studies, and a meta-analysis with high quality of papers is recommended to confirm the association.

References
1. Hengartner MP, Amendola S, Kaminski JA, et al. Suicide risk with selective serotonin reuptake inhibitors and other new-generation antidepressants in adults: a systematic review and meta-analysis of observational studies. J Epidemiol Community Health 2021 Mar 8. doi: 10.1136/jech-2020-214611. [Epub ahead of print]
2. Sharma T, Guski LS, Freund N, et al. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 2016;352:i65.
3. Hengartner MP, Plöderl M. Newer-generation antidepressants and suicide risk in randomized controlled trials: A re-analysis of the FDA database. Psychother Psychosom 2019;88(4):247-248.
4. Kaminski JA, Bschor T. Antidepressants and suicidality: A re-analysis of the re-analysis. J Affect Disord 2020;266:95-99.

The question “Why does Russia have such high cardiovascular (CV) mortality rates?”1 can be answered by a pathologist who practiced during the Soviet time.2 Since then, the quality of post mortem examinations has decreased especially during the 1990s: autopsies were sometimes made perfunctorily. The deterioration in anatomic pathology and the health care in general during the 1990s coincided with the increase in the registered CV mortality. A tendency to over-diagnose CV diseases is generally known to exist also for people dying at home and not undergoing autopsy. If a cause of death is not entirely clear, it has been usual to write on a death certificate: “Ischemic heart disease with cardiac insufficiency” or a similar formulation.2 Concerning the relatively high CV mortality in Russia, it should be commented that irregular treatment of hypertension,3 diabetes and other chronic diseases continues to be a problem. Considering the above, the differences between Norwegian and Russian cohorts1 can be better understood. The levels of serum lipids were comparable between Russia and Norway being slightly higher in the latter possibly due to better nutrition. Interestingly, N-terminal pro-b-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and high-sensitivity C-reactive protein (hsCRP) were higher in Russia.1 It can be reasonably assumed that average levels of these markers inversely correlate with a nation’s health reflected by the life expectancy at birth. Indeed, elevated C-reactive protein is known to be associated with various inflammatory conditions. The natriuretic peptide (NP) plays an important role by opposing the vasoconstriction and sodium retention. A plasma NP elevation was found in essential hypertension, decreasing with effective antihypertensive therapy.4 Hs-cTnT is a biomarker for myocardial damage; but other conditions are also associated with its enhanced level: diabetes, COPD, decreased renal function, anaemia etc.5 The insufficient access to modern healthcare,1 higher consumption of alcohol and cigarettes in Russia vs. Norway (the data can be found in Wikipedia), as well as relatively poor quality of alcohol sold in Russia,6 have probably contributed to a higher morbidity. In conclusion, the valuable results by Dr. Iakunchykova and co-workers1 should motivate further search for associations between NT-proBNP, hs-cTnT and other markers with various pathological conditions.
REFERENCES
1. Iakunchykova O, Averina M, Wilsgaard T, et al. Why does Russia have such high cardiovascular mortality rates? Comparisons of blood–based biomarkers with Norway implicate non-ischaemic cardiac damage. J Epidemiol Community Health 2020;74:698–704.
2. Jargin SV. Cardiovascular mortality trends in Russia: possible mechanisms. Nat Rev Cardiol 2015;12:740.
3. Roberts B, Stickley A, Balabanova D, et al. The persistence of irregular treatment of hypertension in the former Soviet Union. J Epidemiol Community Health 2012;66:1079–82.
4. Hu W, Zhou PH, Zhang XB, Xu CG, Wang W. Plasma concentrations of adrenomedullin and natriuretic peptides in patients with essential hypertension. Exp Ther Med 2015;9:1901–908.
5. Wu W, Li DX, Wang Q, et al. Relationship between high-sensitivity cardiac troponin T and the prognosis of elderly inpatients with non-acute coronary syndromes. Clin Interv Aging 2018;13:1091–8.
6. Jargin SV. Vodka vs. Fortified Wine in Russia: Retrospective View. Alcohol Alcohol 2015;50:624–5.

Dear Editor,
The authors of “Effects of physical activity calorie equivalent food labelling to reduce food selection and consumption: systematic review and meta-analysis of randomized controlled studies” make a strong claim that PACE food labeling can increase consumer consciousness of calorie consumption and therefore caloric reduction, but perhaps this concept deters true understanding of "healthful eating" and may have larger health implications for those with disordered eating.
There is a growing knowledge that that not all calories are created equal. Different foods may not only have different effects on hunger and satiety but also insulin production, gut microbiome interactions, and de novo lipogenesis in the liver (1). While not all consumers need this level of understanding, but without a basic acknowledgement of food’s qualities- like fats, fiber, sugar, ect- the consumer is lead to believe that calories are the most important determinant in what makes food “healthful.” With PACE food labeling, a consumer is led to believe that an ice cream cone and a handful of nuts, both of which could amount to 200 calories, are “equal.” However, in this comparison, only the nuts are possibly advantageous to people with diabetes and cardiovascular disease (2).
Stripping foods down to solely their caloric energy through PACE food labeling could inadvertently foster unhealthy relationships with food. As stated in the article, PACE labeling could be used to “help the public understand what a calorie means and therefore more able to decide whether the calories are ‘worth it.’” Through directing consumers to regard food as just calories to burn off through exercise, instead of fuel for a person’s body, perhaps consumers will come to regard food as punishment instead of its role as nourishment. Those who could be most affected from this way of thinking are the 30 million individuals living in the US with eating disorders (3,4). While obesity does affect more individuals than eating disorders, this is a population of individuals that should be considered when suggesting policymakers to consider implementation of this labeling system. Eating disorders are characterized by a pervasive thought pattern concerning both weight and food so implementing a labeling system that emphasizes food purging through the form of exercise can be detrimental to the mental health of these unique populations (5). Eating disorders have the highest mortality rate of any mental illness and 1 in 5 anorexia deaths are by suicide (6,7). Not only could PACE food labeling adversely affect those with eating disorders, but through fostering unhealthful relationships with food, they could potentially exacerbate the issue. On the other hand, reducing the risk and/or actual prevalence of obesity and all its related ailments, including psychological stress, is a worthy endeavor.
In conclusion, while the authors of this article review a novel and potentially helpful way to combat the growing obesity epidemic, further studies need to be done to compare PACE against current public health education programs and to investigate potential harm to those with eating disorders prior to policy making.
1) Mozaffarian, D.(2017). Foods, obesity, and diabetes—are all calories created equal?, Nutrition Reviews, Issue Suppl_1 Volume 75, Pages 19–31
2) Allen, L. (2008). Priority Areas for Research on the Intake, Composition, and Health Effects of Tree Nuts and Peanuts, The Journal of Nutrition, Volume 138, Issue 9, Pages 1763S–1765S
3) Hudson, J. I., Hiripi, E., Pope, H. G., & Kessler, R. C. (2007). The prevalence and correlates of eating disorders in the national comorbidity survey replication. Biological Psychiatry, 61(3), 348–358.
4) Le Grange, D., Swanson, S. A., Crow, S. J., & Merikangas, K. R. (2012). Eating disorder not otherwise specified presentation in the US population. International Journal of Eating Disorders, 45(5), 711-718.
5) Dell'Osso, L., Abelli, M., Carpita, B., Pini, S., Castellini, G., Carmassi, C., & Ricca, V. (2016). Historical evolution of the concept of anorexia nervosa and relationships with orthorexia nervosa, autism, and obsessive-compulsive spectrum. Neuropsychiatric disease and treatment, 12, 1651–1660.
6) Smink, F. E., van Hoeken, D., & Hoek, H. W. (2012). Epidemiology of eating disorders: Incidence, prevalence and mortality rates. Current Psychiatry Reports,14, 406-414.
7) Arcelus, J., Mitchell, A. J., Wales, J., & Nielsen, S. (2011). Mortality rates in patients with anorexia nervosa and other eating disorders: a meta-analysis of 36 studies. Archives of General Psychiatry, 68, 724-731.

Davis and colleagues must be commended for their concern about cancer outcomes in patients with mental disorders and for acknowledging the poor quality of research.(1) However, their statement “pre-existing mental disorder have a higher odds of advanced stage cancer at diagnosis “ deserve comment.

Firstly, patients with mental disorders, as all vulnerable populations, have poor access to care, considering either quantitatively or qualitatively, even more for specialized care, whatever it could be. Accordingly, a vertical approach only targeting patients with mental disorders would only be a partial and symptomatic solution A root cause analysis is a prerequisite to expect fixing a systemic failure.

Secondly, the term “pre-existing mental disorder” must be questioned as tobacco and alcohol cause both mental health problems and cancer. There is robust and accumulating evidence that cigarette smoking is a causal risk factor for anxiety, depression and, even severe mental illness such as bipolar disorder.(2) Cessation is associated with reduced depression, anxiety and, improved quality of life. While one can understand most patients are fooled by the immediate effects of smoking on perceived stress (decreasing cerebral pain from nicotine withdrawal), the fact that too many psychiatric setting remain smokehouses question the quality of care.(3) Similarly, in many experience, as a second line specialist for severe alcohol use disorders, many of patients referred to me are treated with antidepressants. Antidepressants have modest, if any, useful effects in depressed drinkers but have a potential to aggravate drinking outcomes (pathological intoxication with marked lost control and, occasionally serious violence, even suicide or homicide).(4) This is a real issue in France: a) the use of alcohol, a most depressive agent, is a public health crisis as in England; b) in contrast to England psychotherapy is not reimbursed by the French mandatory healthcare scheme yet despite the success of the Improving Access to Psychological Therapies programme launched in 2008.

Last, even if a pre-existing mental disorder can to be the main concern, as in patients with schizophrenia, no one must overlook that these patients are 3.5 times more likely to die than the general population due to lung cancer, chronic obstructive pulmonary and cardiovascular diseases. For the main psychiatric cause of death, suicide, whose prevention remains a challenge, standardized mortality ratios is 52/100,000 person-years vs 75 for lung cancer.(5) In contrast, adequate treatment for smoking cessation, psychotherapy and nicotine replacement therapy with the belt and brace strategy (patches plus oral forms to suppress occasional craving, at increasing doses) is most effective, whether there are mental health disorders or not.

1 Davis LE, Bogner E, Coburn NG et al. Stage at diagnosis and survival in patients with cancer and a pre-existing mental illness: a meta-analysis. J Epidemiol Community Health 2020;74:84-94.

2 Vermeulen JM, Wootton RE, Treur JL et al. Smoking and the risk for bipolar disorder: evidence from a bidirectional Mendelian randomisation study. Br J Psychiatry. 2019. Online Sep 17. doi: 10.1192/bjp.2019.202.

3 Evins AE, Cather C, Daumit GL. Smoking cessation in people with serious mental illness. Lancet Psychiatry2019;6:563-564.

4 Braillon A. Alcohol Use Disorders and the Barrel of the Danaids. Alcohol Alcohol 2016;51:774.

5 Gatov E, Rosella L, Chiu M, et al. Trends in standardized mortality among individuals with schizophrenia, 1993–2012: a population-based, repeated cross-sectional study. CMAJ 2017;189:E1177–87.