Title:Vitamin D deficiency among admitted patients with acute stroke: a cross -sectional study at a national referral hospital in Kampala, Uganda.

Transcription

1 Reviewer's report Title:Vitamin D deficiency among admitted patients with acute stroke: a cross -sectional study at a national referral hospital in Kampala, Uganda. Version:2Date:6 May 2015 Reviewer:Andre Renzaho Reviewer's report: The study examined vitamin D deficiency among admitted patients with acute stroke at a national referral hospital in Kampala, Uganda, This cross-sectional study was carried out between October 2012 and March 2013 and included 142 participants. The study addresses a very important issue given that non-communicable diseases account for 2.7-million deaths or 28.6% of all deaths in sub-saharan Africa; and both the prevalence and incidence of stroke in Sub-Saharan Africa have been increasing over the last half century as a result of increased life expectancy, changes in environmental determinants and risk factors; and predominantly due to hypertension. However, it its current form the paper is superficial and has many limitations that need to be addressed before it can be accepted for publication. Below I summarised major revisions required which I believe the authors will appreciate and will help improve the manuscript: Major revisions: I. Introduction The introduction is really lacking and the rationale of the study is not clear. For example, throughout the introduction the authors seem to imply the burden of vitamin D deficiency is solely associated with the lack of sunshine. This proposition is half correct. In actual fact, our recent study showed that it is more to do with the latitude (how far you are from the equator), that is, not all sunlight is created equal, with the sun s ultraviolet B rays (the so-called tanning rays) and the rays that trigger the skin to produce vitamin D) stronger near the equator and weaker at higher latitudes. So the introduction is a bit misleading and lack a bit of the understanding of the vitamin D synthesis. This lack of understanding is leading to the authors making sweeping statement such as studies have found widely varying prevalence of vitamin D deficiency, affecting 9-49% of the normal population in a region well-endowed with round the year sunshine. How far are those countries with a prevalence >20% from the equator? Then there are other issues other than cultural factors (e.g. lack of knowledge)i suggest the authors consult the following key readings when revising the manuscript: T Ruwanpathirana, CM Reid, AJ Owen, DP Fong, U Gowda, AM Renzaho: Assessment of vitamin D and its association with cardiovascular disease risk factors in an adult migrant population: an audit of patient records at a Community Health Centre in Kensington, Melbourne, Australia. BMC cardiovascular disorders 14 (1), 157

2 T Ruwanpathirana, A Owen, A Renzaho, E Zomer, M Gambhir, CM Reid: Can oral vitamin D prevent the cardiovascular diseases among migrants in Australia? Provider perspective using Markov modelling. Clinical and Experimental Pharmacology and Physiology U Gowda, MP Mutowo, BJ Smith, AE Wluka, AMN Renzaho: Vitamin D supplementation to reduce depression in adults: Meta-analysis of Randomised Controlled Trials. Nutrition Asia Pac J Clin Nutr. 2013;22(2): doi: /apjcn Pirrone A1, Capetola T, Riggs E, Renzaho A. Vitamin D deficiency awareness among African migrant women residing in high-rise public housing in Melbourne, Australia: a qualitative study. A Renzaho, C Nowson, A Kaur, JA Halliday, D Fong, J DeSilva: Prevalence of vitamin D insufficiency and risk factors for type 2 diabetes and cardiovascular disease among African migrant and refugee adults in Melbourne. Asia Pacific journal of clinical nutrition 20 (3), Etc. In the introduction, the authors state that Studies in other settings have described higher burden of vitamin D deficiency among acute stroke patients than non- stroke individuals in the same environment (from Line 76). Which settings? How does it differ from their study s setting? If this relationship (vitamin D deficiency and stroke) is known why is their study needed? Can the authors really outline what is known in this respect, where are the gaps, and which gap their study is trying to address? The rationale for the study is not clear at all. Later in the intro they sate that Currently, there are no published studies on the magnitude of vitamin D deficiency in stroke patients in Uganda. This is not a rationale, because whether the literature published in other countries show the same trend then this is simply a duplication of n knowledge. Unless the authors are suggesting that there is inconsistency in studies examining the relationship between Vitamin D deficiency and stroke and the difference varies by region, country etc. hence the need to understand Uganda-specific contexts etc. The introduction summarise the consequences of vitamin D deficiency including its effects on bone and its association with infectious diseases like tuberculosis, and non-communicable diseases such as cancer, 75 cardiovascular diseases, and stroke. They are selective in reporting the consequence of vitamin D deficiency. How about mental health such as depression, dementia or multiple sclerosis? Etc. See some the suggested readings above II. Methods Their definition of Vitamin D deficiency is wrong. And if the prevalence was computed as stated then all the results will be wrong. Although still a controversially debated issue, the recently accepted cut-off points are for defining vitamin D deficiency are: Insufficient nmol/l (20-40 ng/ml) ; Mild nmol/l (10 20 ng/ml); Moderate nmol/l (5-10 ng/ml); and Severe < 12.5 nmol/l (< 5 ng/ml) (see for example: Stroud ML, Stilgoe S, Stott VE,

3 Alhabian O, Salman K "Vitamin D a review". Australian Family Physician, 2008; 37 (12): ). Now the cut-off points used by the authors are From Line 120: Vitamin D insufficiency, vitamin D deficiency and severe vitamin D deficiency, were defined as serum 25(OH) D # concentrations ng/ml, # 20 ng/ml, and < 10 ng/ml respectively. Normal vitamin D levels were defined as serum 25(OH)D # 30 ng/ml which are different from the above. Even if we accept their cut-off points could be backed up by the reference, they are still wrong e.g. 25(OH) D # concentrations ng/ml and 25(OH)D # 30 ng/ml are not mutually exclusive, as 30 is already included into 25(OH) D # concentrations ng/ml unless they mean 25(OH) D concentrations #21 but <29 ng/ml or between 21 and 29 ng/ml etc. Similarly, the expression, 25(OH)D # 20 ng/ml, and < 10 ng/ml are not mutually exclusive as <10 is included into 25(OH)D # 20 ng/ml, also their nomenclature does not make sense e.g. vitamin D deficiency vs. severe vitamin D deficiency. Do they mead moderate vs. severe etc. Clarity needed, otherwise the cut-off points and nomenclature do not make sense The sampling of participants is not clear. The authors note that Adults (aged.18 years) admitted to the medical wards with a diagnosis of acute stroke made by the ward team were approached for the study. What is not clear is whether all patients with stroke admitted at the hospital were approached, or whether the approach followed any sampling strategy (e.g. random, systematic, convenient whatever). Regardless of the sampling method used a response rate needs to be provided Questionnaire was used to obtain socio-demographic characteristics, medical history (history of hypertension, diabetes mellitus, HIV), drug history (anti-convulsants, antiretroviral therapy, multi-vitamin supplements, and anti-tuberculous drugs), exercise and estimated duration spent outdoors on a typical day. Why couldn t blood pressure be measured? Why couldn t diabetes be determined by blood test? Etc. also lipid profiles were included but unfortunately the participants were not fasted. Meaning some of the findings on the relationship between vitamin D deficiency and lipid profile are meaningless. Lipid profile from non-fasting participants should be limited to the total cholesterol and HDL cholesterol because the amount of the bad cholesterol such as LDL cholesterol and triglycerides are affected by the foods recently consumed. In other words, while studies have shown that lipids, lipoproteins and apolipoproteins are not much different between fasting and non-fasting samples, with the exception of LDL-Cholesterol and triglycerides, meaning that a fasting sample is preferred if cardiovascular disease risk assessment is based on total cholesterol, LDL cholesterol or non-hdl cholesterol but HDL cholesterol, triglycerides, total/hdl cholesterol ratio. These are serious issues the authors have not clearly justified in the methodology Results

4 The numbers do not add up. They note Vitamin D deficiency was present in 21 (14.8%) patients, of whom 5(3.5%) had severe vitamin D deficiency. Vitamin D insufficiency was noted in 29 (20.4%) of the patients. Overall, 64.8% of the patients had adequate vitamin D. If vitamin D insufficiency was 20.4% and adequate 64.8%, what is the rest (14.8%)? The sentence should be revised (after recalculation as follows: Two thirds (64.8%) of participants had adequate vitamin D status and 35.2% had vitamin D insufficiency. Of those with vitamin D insufficiency XXX had,mild, XX had moderate and XX had severe or The prevalence of mild, moderate and severe vitamin D deficiency was XXX, XXX, and XXX respectively, suggesting that approximate 35.2% were vitamin D insufficient etc. The authors note The burden of vitamin D deficiency was greater among patients with ischemic stroke than in patients with hemorrhagic strokes, although not statistically 210 significant (18% vs. 7%, p=0.33). This is a big difference not to be significant, and I guess that the difference between the strokes could be explained by age (given African get stroke at young age), so I would have preferred to a see an age-standardised/adjusted prevalence reported than the unadjusted prevalence Data in Table 3 do not show what has been adjusted for and the adjusted or ratio column has many missing data. If we accept that diabetes or blood pressure are risk factors for cardio and cerebrovascular diseases, why not adjust for them. The analytical approach is really not clear and the methods of adjustment needs to be made clarer III. Discussion It is good to see the authors comparing their prevalence with the international studies, but to what extent these rates are comparable if they used different cut-off points when defining the deficiency? This is a more important issue to discuss rather than the straight discussion on how their findings compare with the literature Minor revision: The title is misleading as the study actually is not looking at the relationship between vitamin D and stroke. I propose the following: Characterization of vitamin D deficiency and its determinants among admitted patients with acute stroke at a national referral hospital in Kampala, Uganda The abstract does not even state the aim of the study Level of interest:an article whose findings are important to those with closely related research interests Quality of written English:Acceptable Statistical review:yes, and I have assessed the statistics in my report.

5 Declaration of competing interests: None to declare