Aslam et al. conducted a prospective study to assess the association between milk/total dairy consumption and major osteoporotic fracture (MOF) in women (1). The authors handled women aged ≥50 years, and MOFs (hip, forearm, clinical spine and proximal humerus) were confirmed radiologically. Consuming >500 mL/d of milk was not significantly associated with increased HR for MOF. In addition, adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of Non-milk drinkers against drinkers consuming <250 mL/d of milk and consumption of ≥800 g/d total dairy against 200-399 g/d of total dairy for MOF were 1.56 (0.99 to 2.46) and 1.70 (0.99 to 2.93), respectively. They concluded that there was a trend for increased MOF in women with zero milk and higher total dairy consumption. I want to present results from recent meta-analyses.
Malmir et al. summarized the association of milk and dairy intake with risk of osteoporosis and hip fracture (2). There was an inverse relationship of milk and dairy intake with risk of osteoporosis and hip fracture in cross-sectional and case-control studies. By meta-regression analysis, every additional 200-gram intake of dairy and milk were associated with a 22% and 37% reduced risk of osteoporosis, respectively. In addition, milk consumption was associated with a 25% reduced risk of hip fracture. In contrast, the significance disappeared in cohort studies, and a greater intake of milk and dairy products did not reduce the risk of osteo...
Aslam et al. conducted a prospective study to assess the association between milk/total dairy consumption and major osteoporotic fracture (MOF) in women (1). The authors handled women aged ≥50 years, and MOFs (hip, forearm, clinical spine and proximal humerus) were confirmed radiologically. Consuming >500 mL/d of milk was not significantly associated with increased HR for MOF. In addition, adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of Non-milk drinkers against drinkers consuming <250 mL/d of milk and consumption of ≥800 g/d total dairy against 200-399 g/d of total dairy for MOF were 1.56 (0.99 to 2.46) and 1.70 (0.99 to 2.93), respectively. They concluded that there was a trend for increased MOF in women with zero milk and higher total dairy consumption. I want to present results from recent meta-analyses.
Malmir et al. summarized the association of milk and dairy intake with risk of osteoporosis and hip fracture (2). There was an inverse relationship of milk and dairy intake with risk of osteoporosis and hip fracture in cross-sectional and case-control studies. By meta-regression analysis, every additional 200-gram intake of dairy and milk were associated with a 22% and 37% reduced risk of osteoporosis, respectively. In addition, milk consumption was associated with a 25% reduced risk of hip fracture. In contrast, the significance disappeared in cohort studies, and a greater intake of milk and dairy products did not reduce the risk of osteoporosis and hip fracture. These results were statistically consistent with data by Aslam et al.
Hidayat et al. evaluated the association between dairy consumption (milk, yogurt, and cheese) and the risk of hip fracture (3). Pooled relative risks (RRs) (95% CIs) of the highest versus lowest category of yogurt, milk, and cheese consumptions for hip fracture were 0.78 (0.68 to 0.90), 0.86 (0.73 to 1.02), and 0.85 (0.66 to 1.08), respectively. Protective effect of milk consumption for hip fracture was only observed in USA study, presenting pooled RR (95% CI) of 0.75 (0.65 to 0.87). The study in USA also presented that pooled RR (95% CI) of milk consumption per 1 glass/day for hip fracture was 0.93 (0.88 to 0.98). Discrepancy of results in different countries and different types of dairy products might need further study to verify the association. Stratified meta-analysis by sex and age are recommended, such as women aged ≥50 years old (1).
References
1. Aslam H, Holloway-Kew KL, Mohebbi M, Jacka FN, Pasco JA. Association between dairy intake and fracture in an Australian-based cohort of women: a prospective study. BMJ Open. 2019;9(11):e031594. Published 2019 Nov 21. doi:10.1136/bmjopen-2019-031594
2. Malmir H, Larijani B, Esmaillzadeh A. Consumption of milk and dairy products and risk of osteoporosis and hip fracture: a systematic review and Meta-analysis. Crit Rev Food Sci Nutr. 2020;60(10):1722‐1737. doi:10.1080/10408398.2019.1590800
3. Hidayat K, Du X, Shi BM, Qin LQ. Systematic review and meta-analysis of the association between dairy consumption and the risk of hip fracture: critical interpretation of the currently available evidence. Osteoporos Int. 2020 May 7. doi:10.1007/s00198-020-05383-3
Cooper et al. investigated clinical predictors of mortality in adults with intellectual disabilities (1). Standardized mortality ratios (SMRs) (95% confidence interval [CI]) in Down syndrome adults and adults without Down syndrome were 5.28 (3.98, 6.57) and 1.93 (1.68, 2.18), respectively. In addition, SMRs in males and females were 1.69 (1.42, 1.95) and 3.48 (2.90, 4.06), respectively. Aspiration/reflux/choking and respiratory infection were the most common causes of mortality in adults without Down syndrome, and dementia was the most common causes of mortality in Down syndrome adults. Mortality risk related to percutaneous endoscopic gastrostomy/tube fed, Down syndrome, diabetes, lower respiratory tract infection at cohort-entry, smoking, epilepsy, hearing impairment, increasing number of prescribed drugs, increasing age were related to mortality in adults with intellectual disabilities. I have some concerns about their study.
First, Oppewal et al. also reported the cause-specific mortality of older Down syndrome adults with intellectual disability (2). The common cause of mortality was respiratory disease (51.1%), followed by dementia (22.2%), and this information was not consistent with data by Cooper et al. Methodological difference of survey, including definition, might contribute to the statistical information.
Second, de Campos Gomes et al. analyzed mortality and related factors in individuals with Down syndrome in Brazil (3). They concluded that ethn...
Cooper et al. investigated clinical predictors of mortality in adults with intellectual disabilities (1). Standardized mortality ratios (SMRs) (95% confidence interval [CI]) in Down syndrome adults and adults without Down syndrome were 5.28 (3.98, 6.57) and 1.93 (1.68, 2.18), respectively. In addition, SMRs in males and females were 1.69 (1.42, 1.95) and 3.48 (2.90, 4.06), respectively. Aspiration/reflux/choking and respiratory infection were the most common causes of mortality in adults without Down syndrome, and dementia was the most common causes of mortality in Down syndrome adults. Mortality risk related to percutaneous endoscopic gastrostomy/tube fed, Down syndrome, diabetes, lower respiratory tract infection at cohort-entry, smoking, epilepsy, hearing impairment, increasing number of prescribed drugs, increasing age were related to mortality in adults with intellectual disabilities. I have some concerns about their study.
First, Oppewal et al. also reported the cause-specific mortality of older Down syndrome adults with intellectual disability (2). The common cause of mortality was respiratory disease (51.1%), followed by dementia (22.2%), and this information was not consistent with data by Cooper et al. Methodological difference of survey, including definition, might contribute to the statistical information.
Second, de Campos Gomes et al. analyzed mortality and related factors in individuals with Down syndrome in Brazil (3). They concluded that ethnic factors and years of schooling influenced mortality across the administrative regions. Different region has ethnic difference and different races, which would contribute to educational difference and medical service. These factors would relate each other, and contribute mortality in individuals with Down syndrome.
Regarding complication in Down syndrome, congenital heart defects (CHDs) should be classified to typical and atypical CHDs for mortality risk (4). Atypical CHDs include aortic coarctation and univentricular hearts, and survival rate at 10 and 40 years in patients with typical CHDs were 99% and 98%, which were significantly higher than those in patients with atypical CHDs, presenting 91% and 84%. Complication might contribute to prognosis in individuals of Down syndrome, which had been also recognized (1, 5).
Finally, Hithersay et al. examined factors associated with dementia in Down syndrome adults (6). Hazard ratio (HR) (95% CI) of APOE ε4 carriers for mortality in Down syndrome adults with dementia was 6.91 (1.756, 27.195). In addition, HR (95% CI) of epilepsy for mortality in Down syndrome adults without dementia was 9.66 (1.59, 58.56). Furthermore, HRs (95% CIs) of APOE ε4 carriers, adults with early-onset epilepsy, multiple health comorbidities, and those living with family for earlier dementia diagnoses were 4.91 (2.53, 9.56), 3.61 (1.12, 11.60), 1.956 (1.087, 3.519), and 2.14 (1.08, 4.20), respectively. Dementia was the most common causes of mortality in Down syndrome adults (1), and factors of earlier dementia diagnoses were specified.
References
1. BMJ Open. 2020;10(5):e036465. doi:10.1136/bmjopen-2019-036465
2. Am J Intellect Dev Disabil. 2018;123(1):61-71. doi:10.1352/1944-7558-123.1.61
3. J Intellect Disabil Res. 2020 May 7. doi:10.1111/jir.12735
4. Am J Med Genet A. 2020 Apr 22. doi:10.1002/ajmg.a.61586
5. J Appl Res Intellect Disabil. 2020;33(3):420-429. doi:10.1111/jar.12684
6. JAMA Neurol. 2019;76(2):152-160. doi:10.1001/jamaneurol.2018.3616
Lycett et al. conducted an important intervention to avoid obesity in quitting smokers (1). There is a brain mechanism on the relationship between stop smoking and subsequent weight gain. Dietary modification is important, but food restriction is closely associated with stress and causes relapse of smoking. A commercial weight management program plus stop smoking support (treatment group) was compared with stop smoking support alone (control group) for the change in weight (kg) at 12 weeks. At 12 weeks weight gain was less in the treatment than the control group with an adjusted mean difference (95% CI) of -2.3 kg (-4.4 to -0.1). Craving scores were lower (Mood and Physical Symptoms Scale craving domain -1.6 (95%CI: -2.7 to -0.5)) and quit rates were higher in the treatment than the control group (32% vs 21%). Unfortunately, this trial could not present statistical superiority in cravings and quit rates. I have two concerns about their study.
First, I previously reported that increased body mass index in quitting smokers had a tendency of decreasing after 8 years (2), although inconsistent results have also been reported (3). Anyway, continuous weight monitoring is important in quitting smokers (4).
Second, relapse of smoking also happens after 12 weeks in their everyday life. Especially drinking habits should be paid with caution. In addition, risk assessment of weight gain by quitting different types of cigarette, heat-not-burn/e-cigarette, is needed (5)....
Lycett et al. conducted an important intervention to avoid obesity in quitting smokers (1). There is a brain mechanism on the relationship between stop smoking and subsequent weight gain. Dietary modification is important, but food restriction is closely associated with stress and causes relapse of smoking. A commercial weight management program plus stop smoking support (treatment group) was compared with stop smoking support alone (control group) for the change in weight (kg) at 12 weeks. At 12 weeks weight gain was less in the treatment than the control group with an adjusted mean difference (95% CI) of -2.3 kg (-4.4 to -0.1). Craving scores were lower (Mood and Physical Symptoms Scale craving domain -1.6 (95%CI: -2.7 to -0.5)) and quit rates were higher in the treatment than the control group (32% vs 21%). Unfortunately, this trial could not present statistical superiority in cravings and quit rates. I have two concerns about their study.
First, I previously reported that increased body mass index in quitting smokers had a tendency of decreasing after 8 years (2), although inconsistent results have also been reported (3). Anyway, continuous weight monitoring is important in quitting smokers (4).
Second, relapse of smoking also happens after 12 weeks in their everyday life. Especially drinking habits should be paid with caution. In addition, risk assessment of weight gain by quitting different types of cigarette, heat-not-burn/e-cigarette, is needed (5).
References
1. Lycett D, Aveyard P, Farmer A, et al. Referral to Slimming World in UK Stop Smoking Services (SWISSS) versus stop smoking support alone on body weight in quitters: results of a randomised controlled trial. BMJ Open. 2020;10(1):e032271. doi: 10.1136/bmjopen-2019-032271
2. Kawada T. Difference of body mass index stratified by the period of smoking cessation from a cross-sectional study. Arch Med Res. 2004;35(2):181-184.
3. Jain P, Danaei G, Robins JM, et al. Smoking cessation and long-term weight gain in the Framingham Heart Study: an application of the parametric g-formula for a continuous outcome. Eur J Epidemiol. 2016;31(12):1223-1229.
4. O'Hara P, Connett JE, Lee WW, et al. Early and late weight gain following smoking cessation in the Lung Health Study. Am J Epidemiol. 1998;148(9):821-830.
5. Lee Y, Lee KS. Association of alcohol and drug use with use of electronic cigarettes and heat-not-burn tobacco products among Korean adolescents. PLoS One. 2019;14(7):e0220241. doi: 10.1371/journal.pone.0220241
Pratt et al. compared effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin (1). There was no significant difference in the risk of ischaemic stroke or bleeding between low-strength DOACs and warfarin. No increase of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban. For high-strength DOACs, no difference was found for ischaemic stroke, however, there was a significant reduction in risk of bleeding events and death, presenting hazard ratios (HRs) (95% confidence intervals [CIs]) of 0.63 (0.44 to 0.89) and 0.40 (0.28 to 0.58), respectively. I have two concerns about their study.
First, Xian et al. examined the clinical effectiveness of DOACs against warfarin prescription at discharge after ischemic stroke in patients with atrial fibrillation (AF) (2). Adjusted HR (99% CI) of patients receiving DOACs for major adverse cardiovascular events was 0.89 (0.83-0.96). Other events were also significantly decreased in patients receiving DOACs, except gastrointestinal bleeding. The authors concluded that DOAC use at discharge was significantly associated with better long-term outcomes relative to warfarin. Pratt et al. classified DOACs into two dosages, and specified some different outcomes on effectiveness and safety. I suppose that randomized trials are needed to verify the effectiveness and safety of DOACs.
Second, Pham et al. evaluated the risk of bleeding with DOACs...
Pratt et al. compared effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin (1). There was no significant difference in the risk of ischaemic stroke or bleeding between low-strength DOACs and warfarin. No increase of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban. For high-strength DOACs, no difference was found for ischaemic stroke, however, there was a significant reduction in risk of bleeding events and death, presenting hazard ratios (HRs) (95% confidence intervals [CIs]) of 0.63 (0.44 to 0.89) and 0.40 (0.28 to 0.58), respectively. I have two concerns about their study.
First, Xian et al. examined the clinical effectiveness of DOACs against warfarin prescription at discharge after ischemic stroke in patients with atrial fibrillation (AF) (2). Adjusted HR (99% CI) of patients receiving DOACs for major adverse cardiovascular events was 0.89 (0.83-0.96). Other events were also significantly decreased in patients receiving DOACs, except gastrointestinal bleeding. The authors concluded that DOAC use at discharge was significantly associated with better long-term outcomes relative to warfarin. Pratt et al. classified DOACs into two dosages, and specified some different outcomes on effectiveness and safety. I suppose that randomized trials are needed to verify the effectiveness and safety of DOACs.
Second, Pham et al. evaluated the risk of bleeding with DOACs and verapamil or diltiazem in patients with AF (3). HRs for the overall bleeding and gastrointestinal bleeding by setting amlodipine or metoprolol as a control significantly increased. Although there is a better efficacy for the combination use of DOACs and P-glycoprotein for the prevention of cerebral infarction, a risk of gastrointestinal bleeding by DOACs increased by the combination with P-glycoprotein. Strategies of keeping safety for the use of DOACs are required.
References
1. Pratt NL, Ramsay E, Kalisch Ellett LM, et al. Comparative effectiveness and safety of low-strength and high-strength direct oral anticoagulants compared with warfarin: a sequential cohort study. BMJ Open. 2019;9(5):e026486. doi: 10.1136/bmjopen-2018-026486
2. Xian Y, Xu H, O'Brien EC, et al. Clinical effectiveness of direct oral anticoagulants vs warfarin in older patients with atrial fibrillation and ischemic stroke: Findings from the patient-centered research into outcomes stroke patients prefer and effectiveness research (PROSPER) study. JAMA Neurol. 2019 Jul 22. doi: 10.1001/jamaneurol.2019.2099
3. Pham P, Schmidt S, Lesko L, et al. Association of oral anticoagulants and verapamil or diltiazem with adverse bleeding events in patients with nonvalvular atrial fibrillation and normal kidney function. JAMA Netw Open. 2020;3(4):e203593. doi: 10.1001/jamanetworkopen.2020.3593
Update: This systematic review was registered with PROSPERO on April 28, 2020. Registration number: CRD42020159050. Registration was submitted on November, 18, 2019.
Cho et al. investigated the combined effect of exposure to perceived risk at work and unstable employment on self-rated health (1). Among Korean employees, odds ratios (ORs) (95% confidence intervals [CIs]) of perceived risk at work and unstable employment for poor self-rated health were 2.00 (1.80 to 2.22) and 1.18 (1.09 to 1.28), respectively. In addition, OR (95% CI) of both perceived risk at work and unstable employment for poor self-rated health was 3.22 (2.72 to 3.81), and relative excess risk due to interaction (RERI) (95% CI) was 1.03 (0.48 to 1.58). Among European employees, ORs (95% CIs) of perceived risk at work and unstable employment for poor self-rated health were 3.20 (2.93 to 3.49) and 1.04 (0.97 to 1.13), respectively. In addition, OR (95% CI) of both perceived risk at work and unstable employment for poor self-rated health was 3.41 (2.93 to 3.98), and RERI (95% CI) was 0.18 (-0.36 to 0.71).There was a supra-additive interaction between perceived risk at work and unstable employment on poor self-rated health among Korean employees, and I have a query about data among Korean employees.
Kim et al. reported that odds ratio of precarious employment for poor health was marginally significant, by adjusting socio-demographic covariates, job satisfaction, job insecurity, and monthly wage (2). Kwon et al. also evaluated the association between employment status and self-rated health (3). The percentage of non-permanent workers was 20.8 %, and OR of non-perma...
Cho et al. investigated the combined effect of exposure to perceived risk at work and unstable employment on self-rated health (1). Among Korean employees, odds ratios (ORs) (95% confidence intervals [CIs]) of perceived risk at work and unstable employment for poor self-rated health were 2.00 (1.80 to 2.22) and 1.18 (1.09 to 1.28), respectively. In addition, OR (95% CI) of both perceived risk at work and unstable employment for poor self-rated health was 3.22 (2.72 to 3.81), and relative excess risk due to interaction (RERI) (95% CI) was 1.03 (0.48 to 1.58). Among European employees, ORs (95% CIs) of perceived risk at work and unstable employment for poor self-rated health were 3.20 (2.93 to 3.49) and 1.04 (0.97 to 1.13), respectively. In addition, OR (95% CI) of both perceived risk at work and unstable employment for poor self-rated health was 3.41 (2.93 to 3.98), and RERI (95% CI) was 0.18 (-0.36 to 0.71).There was a supra-additive interaction between perceived risk at work and unstable employment on poor self-rated health among Korean employees, and I have a query about data among Korean employees.
Kim et al. reported that odds ratio of precarious employment for poor health was marginally significant, by adjusting socio-demographic covariates, job satisfaction, job insecurity, and monthly wage (2). Kwon et al. also evaluated the association between employment status and self-rated health (3). The percentage of non-permanent workers was 20.8 %, and OR of non-permanent workers for poor self-rated health was 1.20 by adjusting socio-demographic factors, work environment and work hazards. Kwon et al. used non-permanent work and work hazards independently used and interaction of two parameters on poor self-rated health was not consider as Cho et al. evaluated. Anyway, prospective analysis is needed to speculate the causal association.
References
1. Cho SS, Paek D, Kang MY. Influence of combined exposure to perceived risk at work and unstable employment on self-rated health: a comparison of two cross-sectional surveys in Europe and Korea. BMJ Open. 2020;10(1):e032380. doi: 10.1136/bmjopen-2019-032380
2. Kim MH, Kim CY, Park JK, et al. Is precarious employment damaging to self-rated health? Results of propensity score matching methods, using longitudinal data in South Korea. Soc Sci Med. 2008;67(12):1982-94. doi: 10.1016/j.socscimed.2008.09.051
3. Kwon K, Park JB, Lee KJ, et al. Association between employment status and self-rated health: Korean working conditions survey. Ann Occup Environ Med. 2016;28(1):43. doi: 10.1186/s40557-016-0126-z
Saji et al. intended a prospective study to know the effects of warfarin therapy and direct oral anticoagulants (DOACs) on cerebrovascular diseases and cognitive impairment (CI) in patients with non-valvular atrial fibrillation (NVAF) over an estimated duration of 36 months (1). I want to present some information.
First, Mongkhon et al. investigated the risk of dementia/CI among newly diagnosed atrial fibrillation (AF) patients with and without oral anticoagulation (OAC) treatment over a mean follow-up of 5.9 years (2). Hazard ratios (HRs) (95% confidence intervals [CIs) of OAC treatment and antiplatelets for dementia/CI were 0.90 (0.85-0.95) and 0.84 (0.79-0.90), respectively. In contrast, HR (95% CI) of DOACs treatment against warfarin for dementia/CI was 0.89 (0.70-1.14). Furthermore, HR (95% CI) of dual therapy (OAC plus antiplatelets) for dementia/CI was 1.17 (1.05-1.31). Saji et al. set two clinical outcomes, and study period was shorter. In addition, safety evaluation on bleeding might also be required.
Second, Diener et al. recommended randomized trials to evaluate whether OAC, including warfarin and DOACs, reduces dementia/CI in AF patients (3). Dementia/CI, including vascular dementia and Alzheimer's disease, might be related to ischemic stroke, cerebral micro-infarcts, cerebral hemorrhage, and reduced cerebral blood flow. Taken together, risk assessment of medications for dementia/CI in AF patients would be closely associated with types of cer...
Saji et al. intended a prospective study to know the effects of warfarin therapy and direct oral anticoagulants (DOACs) on cerebrovascular diseases and cognitive impairment (CI) in patients with non-valvular atrial fibrillation (NVAF) over an estimated duration of 36 months (1). I want to present some information.
First, Mongkhon et al. investigated the risk of dementia/CI among newly diagnosed atrial fibrillation (AF) patients with and without oral anticoagulation (OAC) treatment over a mean follow-up of 5.9 years (2). Hazard ratios (HRs) (95% confidence intervals [CIs) of OAC treatment and antiplatelets for dementia/CI were 0.90 (0.85-0.95) and 0.84 (0.79-0.90), respectively. In contrast, HR (95% CI) of DOACs treatment against warfarin for dementia/CI was 0.89 (0.70-1.14). Furthermore, HR (95% CI) of dual therapy (OAC plus antiplatelets) for dementia/CI was 1.17 (1.05-1.31). Saji et al. set two clinical outcomes, and study period was shorter. In addition, safety evaluation on bleeding might also be required.
Second, Diener et al. recommended randomized trials to evaluate whether OAC, including warfarin and DOACs, reduces dementia/CI in AF patients (3). Dementia/CI, including vascular dementia and Alzheimer's disease, might be related to ischemic stroke, cerebral micro-infarcts, cerebral hemorrhage, and reduced cerebral blood flow. Taken together, risk assessment of medications for dementia/CI in AF patients would be closely associated with types of cerebral disease and its progression. A meta-analysis of randomized trials would finally present reliable information.
References
1. Saji N, Sakurai T, Ito K, et al. Protective effects of oral anticoagulants on cerebrovascular diseases and cognitive impairment in patients with atrial fibrillation: protocol for a multicentre, prospective, observational, longitudinal cohort study (Strawberry study). BMJ Open. 2018;8(11):e021759. doi: 10.1136/bmjopen-2018-021759
2. Mongkhon P, Fanning L, Lau WCY, et al. Oral anticoagulant and reduced risk of dementia in patients with atrial fibrillation: A population-based cohort study. Heart Rhythm. 2020 Jan 10. doi: 10.1016/j.hrthm.2020.01.007
3. Diener HC, Hart RG, Koudstaal PJ, et al. Atrial fibrillation and cognitive function: JACC review topic of the week. J Am Coll Cardiol. 2019;73(5):612-619. doi: 10.1016/j.jacc.2018.10.077
We thank Dr. Elizabeth A Pritts, Dr. David L Olive, and Dr. William H. Parker for their great interest in our study and for the very qualified comments. To investigate the influence of uterine fibroids on obstetrical outcomes is complex and can be viewed from different angles. - We aimed to investigate symptomatic uterine fibroids. Well conducted cohort studies are the best available substitutes when experiments are not possible. Methodological limitations need to be taken into consideration, and associations can be explored. We are fully aware that limitations must be relevantly discussed. David A Grimes 1 pointed out some important issues regarding cohort studies:
1) The exposure should be clear: we argue to have a clearly defined exposure.
2) The importance of potential confounders: we have been able to include important confounders using the directed acyclic graph, DAG.
3) Awareness that the risk of a weak association (HR 0.5-2) is likely to be due to bias and not causation: We have clearly stated that we have found associations and further that the association could be interesting for further research, but we do not recommend changes in clinical recommendations.
The risks of misclassification of exposure were related to the uterine fibroid diagnoses codes. The daily clinical coding may be incorrect or lacking due to various work-related distractions or variable individual interpretation of clinical cases. The low prevalence of uterine fibroids...
We thank Dr. Elizabeth A Pritts, Dr. David L Olive, and Dr. William H. Parker for their great interest in our study and for the very qualified comments. To investigate the influence of uterine fibroids on obstetrical outcomes is complex and can be viewed from different angles. - We aimed to investigate symptomatic uterine fibroids. Well conducted cohort studies are the best available substitutes when experiments are not possible. Methodological limitations need to be taken into consideration, and associations can be explored. We are fully aware that limitations must be relevantly discussed. David A Grimes 1 pointed out some important issues regarding cohort studies:
1) The exposure should be clear: we argue to have a clearly defined exposure.
2) The importance of potential confounders: we have been able to include important confounders using the directed acyclic graph, DAG.
3) Awareness that the risk of a weak association (HR 0.5-2) is likely to be due to bias and not causation: We have clearly stated that we have found associations and further that the association could be interesting for further research, but we do not recommend changes in clinical recommendations.
The risks of misclassification of exposure were related to the uterine fibroid diagnoses codes. The daily clinical coding may be incorrect or lacking due to various work-related distractions or variable individual interpretation of clinical cases. The low prevalence of uterine fibroids in our study population is likely to be a result of underreporting, or due to DNBC representing a selected group of women.
Specific diagnosis codes within the DNPR have been validated with different results. As you correctly point out, several studies have found specific data within the DNPR invalid, but others have in contrast found other data valid and suitable for research 2-7. A detailed validation of the uterine fibroid diagnosis codes was not possible and has not previously been performed. We relied on previous studies that have shown that reproductive gynecological coding in the DNPR is generally valid and suitable for clinical quality control 8. Further, we made it clear that we investigated a specific group of women with symptomatic uterine fibroids and not uterine fibroids in general. We cannot completely eliminate the risk that some women got the diagnosis code without symptoms, but we found it unlikely, considering that women in Denmark are mainly examined by ultrasound scan due to symptoms, not a routine basis. If the uterine fibroids were symptomatic and required treatment, we found it likely that the women were given a diagnosis code linked to the treatment code. On these ground we argue that we have investigated a group of women with symptomatic uterine fibroids. Others have defined the exposure based on routine ultrasound scans made in the first trimester of pregnancy, irrespective of symptoms. Symptomatic uterine fibroids might represent another group of fibroids with other associated obstetrical risks.
Participants in cohort studies are often a selected group due to the acceptance of participation and may not fully represent the source population. The DNBC mainly consists of white women with middle or high social status 9. We are therefore evaluated a selected group of women, which could explain the lower prevalence of uterine fibroid diagnosis codes.
A potential bias will lead towards exposed women being categorized as unexposed. Since the potential underreporting is independent of the outcome because of the prospective nature of data collection in a cohort study, the potential misclassification could have led to non-differential information bias and hence attenuation of the association between exposure (uterine fibroids) and outcomes 10.
Regarding the very relevant comment on our use of robust standard errors we would like to clarify our decision. Some women contributed with more than one pregnancy in the analyses. Hence, we had clustered data, since observations from two different pregnancies in the same woman would tend to be more similar to each other than to individuals in the rest of the sample. By the use of robust standard errors, we corrected the standard errors for the clustering 11, a well-known and appropriate statistical method.
Response to the comment; "The authors state that risk of preterm birth is decreased, and cesarean section rates increased among women with untreated fibroids compared with women with surgical excision. However, this appears to be based upon raw numbers and not statistical analysis, as the two groups (fibroids in situ versus fibroids removed) were never compared"
In the article we wrote that ‘’ In the present study, the risk of preterm birth decreased whereas the risk of CS increased after myomectomy compared with the risks among women with untreated uterine fibroids‘’ We might have added ”insignificantly” to make it clear that none of the formal comparisons between groups 2 and 4 were significant. However, this is evident from the published odds ratios and 95% CIs in table 2. For example, 1.81 (1.24 – 2.65) is clearly not significantly different from 2.27 (1.30 – 3.96).
Future research on uterine fibroids and impact on obstetrical outcome can be approached in different ways. It could include all uterine fibroids as one big group. Uterine fibroids could be identified and number, type and size of the fibroids recorded. Another approach could be to examine women with clinical symptoms of the uterine fibroids. It is possible that these groups of fibroids are different in terms of associated obstetrical outcomes and thereof potentially different in terms of clinical recommendations.
1.Grimes DA. Epidemiologic research with administrative databases: red herrings, false alarms and pseudo-epidemics. Hum Reprod 2015;30(8):1749-52.) 2.Hess DT Jr. The Danish National Patient Register. Surg Obes Relat Dis. 2016 Feb;12(2):304. doi: 10.1016/j.soard.2015.11.001. Epub 2015 Nov 5. 3.Adelborg K, Sundbøll J, Munch T, Frøslev T, Sørensen HT, Bøtker HE, Schmidt M. Positive predictive value of cardiac examination, procedure and surgery codes in the Danish National Patient Registry: a population-based validation study. BMJ Open. 2016 Dec 9;6(12):e012817. doi: 10.1136/bmjopen-2016-012817.
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Very nice work by the authors. Perhaps they could provide additional details about the methods used here to test particle filtration.
Aslam et al. conducted a prospective study to assess the association between milk/total dairy consumption and major osteoporotic fracture (MOF) in women (1). The authors handled women aged ≥50 years, and MOFs (hip, forearm, clinical spine and proximal humerus) were confirmed radiologically. Consuming >500 mL/d of milk was not significantly associated with increased HR for MOF. In addition, adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of Non-milk drinkers against drinkers consuming <250 mL/d of milk and consumption of ≥800 g/d total dairy against 200-399 g/d of total dairy for MOF were 1.56 (0.99 to 2.46) and 1.70 (0.99 to 2.93), respectively. They concluded that there was a trend for increased MOF in women with zero milk and higher total dairy consumption. I want to present results from recent meta-analyses.
Malmir et al. summarized the association of milk and dairy intake with risk of osteoporosis and hip fracture (2). There was an inverse relationship of milk and dairy intake with risk of osteoporosis and hip fracture in cross-sectional and case-control studies. By meta-regression analysis, every additional 200-gram intake of dairy and milk were associated with a 22% and 37% reduced risk of osteoporosis, respectively. In addition, milk consumption was associated with a 25% reduced risk of hip fracture. In contrast, the significance disappeared in cohort studies, and a greater intake of milk and dairy products did not reduce the risk of osteo...
Show MoreCooper et al. investigated clinical predictors of mortality in adults with intellectual disabilities (1). Standardized mortality ratios (SMRs) (95% confidence interval [CI]) in Down syndrome adults and adults without Down syndrome were 5.28 (3.98, 6.57) and 1.93 (1.68, 2.18), respectively. In addition, SMRs in males and females were 1.69 (1.42, 1.95) and 3.48 (2.90, 4.06), respectively. Aspiration/reflux/choking and respiratory infection were the most common causes of mortality in adults without Down syndrome, and dementia was the most common causes of mortality in Down syndrome adults. Mortality risk related to percutaneous endoscopic gastrostomy/tube fed, Down syndrome, diabetes, lower respiratory tract infection at cohort-entry, smoking, epilepsy, hearing impairment, increasing number of prescribed drugs, increasing age were related to mortality in adults with intellectual disabilities. I have some concerns about their study.
First, Oppewal et al. also reported the cause-specific mortality of older Down syndrome adults with intellectual disability (2). The common cause of mortality was respiratory disease (51.1%), followed by dementia (22.2%), and this information was not consistent with data by Cooper et al. Methodological difference of survey, including definition, might contribute to the statistical information.
Second, de Campos Gomes et al. analyzed mortality and related factors in individuals with Down syndrome in Brazil (3). They concluded that ethn...
Show MoreLycett et al. conducted an important intervention to avoid obesity in quitting smokers (1). There is a brain mechanism on the relationship between stop smoking and subsequent weight gain. Dietary modification is important, but food restriction is closely associated with stress and causes relapse of smoking. A commercial weight management program plus stop smoking support (treatment group) was compared with stop smoking support alone (control group) for the change in weight (kg) at 12 weeks. At 12 weeks weight gain was less in the treatment than the control group with an adjusted mean difference (95% CI) of -2.3 kg (-4.4 to -0.1). Craving scores were lower (Mood and Physical Symptoms Scale craving domain -1.6 (95%CI: -2.7 to -0.5)) and quit rates were higher in the treatment than the control group (32% vs 21%). Unfortunately, this trial could not present statistical superiority in cravings and quit rates. I have two concerns about their study.
First, I previously reported that increased body mass index in quitting smokers had a tendency of decreasing after 8 years (2), although inconsistent results have also been reported (3). Anyway, continuous weight monitoring is important in quitting smokers (4).
Second, relapse of smoking also happens after 12 weeks in their everyday life. Especially drinking habits should be paid with caution. In addition, risk assessment of weight gain by quitting different types of cigarette, heat-not-burn/e-cigarette, is needed (5)....
Show MorePratt et al. compared effectiveness and safety of low-strength and high-strength direct oral anticoagulants (DOACs) with warfarin (1). There was no significant difference in the risk of ischaemic stroke or bleeding between low-strength DOACs and warfarin. No increase of myocardial infarction was found for low-strength DOACs, however, risk was elevated for apixaban. For high-strength DOACs, no difference was found for ischaemic stroke, however, there was a significant reduction in risk of bleeding events and death, presenting hazard ratios (HRs) (95% confidence intervals [CIs]) of 0.63 (0.44 to 0.89) and 0.40 (0.28 to 0.58), respectively. I have two concerns about their study.
First, Xian et al. examined the clinical effectiveness of DOACs against warfarin prescription at discharge after ischemic stroke in patients with atrial fibrillation (AF) (2). Adjusted HR (99% CI) of patients receiving DOACs for major adverse cardiovascular events was 0.89 (0.83-0.96). Other events were also significantly decreased in patients receiving DOACs, except gastrointestinal bleeding. The authors concluded that DOAC use at discharge was significantly associated with better long-term outcomes relative to warfarin. Pratt et al. classified DOACs into two dosages, and specified some different outcomes on effectiveness and safety. I suppose that randomized trials are needed to verify the effectiveness and safety of DOACs.
Second, Pham et al. evaluated the risk of bleeding with DOACs...
Show MoreIs my understanding correct in thinking this study was never conducted? I would love to learn more about this!
Update: This systematic review was registered with PROSPERO on April 28, 2020. Registration number: CRD42020159050. Registration was submitted on November, 18, 2019.
Cho et al. investigated the combined effect of exposure to perceived risk at work and unstable employment on self-rated health (1). Among Korean employees, odds ratios (ORs) (95% confidence intervals [CIs]) of perceived risk at work and unstable employment for poor self-rated health were 2.00 (1.80 to 2.22) and 1.18 (1.09 to 1.28), respectively. In addition, OR (95% CI) of both perceived risk at work and unstable employment for poor self-rated health was 3.22 (2.72 to 3.81), and relative excess risk due to interaction (RERI) (95% CI) was 1.03 (0.48 to 1.58). Among European employees, ORs (95% CIs) of perceived risk at work and unstable employment for poor self-rated health were 3.20 (2.93 to 3.49) and 1.04 (0.97 to 1.13), respectively. In addition, OR (95% CI) of both perceived risk at work and unstable employment for poor self-rated health was 3.41 (2.93 to 3.98), and RERI (95% CI) was 0.18 (-0.36 to 0.71).There was a supra-additive interaction between perceived risk at work and unstable employment on poor self-rated health among Korean employees, and I have a query about data among Korean employees.
Kim et al. reported that odds ratio of precarious employment for poor health was marginally significant, by adjusting socio-demographic covariates, job satisfaction, job insecurity, and monthly wage (2). Kwon et al. also evaluated the association between employment status and self-rated health (3). The percentage of non-permanent workers was 20.8 %, and OR of non-perma...
Show MoreSaji et al. intended a prospective study to know the effects of warfarin therapy and direct oral anticoagulants (DOACs) on cerebrovascular diseases and cognitive impairment (CI) in patients with non-valvular atrial fibrillation (NVAF) over an estimated duration of 36 months (1). I want to present some information.
First, Mongkhon et al. investigated the risk of dementia/CI among newly diagnosed atrial fibrillation (AF) patients with and without oral anticoagulation (OAC) treatment over a mean follow-up of 5.9 years (2). Hazard ratios (HRs) (95% confidence intervals [CIs) of OAC treatment and antiplatelets for dementia/CI were 0.90 (0.85-0.95) and 0.84 (0.79-0.90), respectively. In contrast, HR (95% CI) of DOACs treatment against warfarin for dementia/CI was 0.89 (0.70-1.14). Furthermore, HR (95% CI) of dual therapy (OAC plus antiplatelets) for dementia/CI was 1.17 (1.05-1.31). Saji et al. set two clinical outcomes, and study period was shorter. In addition, safety evaluation on bleeding might also be required.
Second, Diener et al. recommended randomized trials to evaluate whether OAC, including warfarin and DOACs, reduces dementia/CI in AF patients (3). Dementia/CI, including vascular dementia and Alzheimer's disease, might be related to ischemic stroke, cerebral micro-infarcts, cerebral hemorrhage, and reduced cerebral blood flow. Taken together, risk assessment of medications for dementia/CI in AF patients would be closely associated with types of cer...
Show MoreWe thank Dr. Elizabeth A Pritts, Dr. David L Olive, and Dr. William H. Parker for their great interest in our study and for the very qualified comments. To investigate the influence of uterine fibroids on obstetrical outcomes is complex and can be viewed from different angles. - We aimed to investigate symptomatic uterine fibroids. Well conducted cohort studies are the best available substitutes when experiments are not possible. Methodological limitations need to be taken into consideration, and associations can be explored. We are fully aware that limitations must be relevantly discussed. David A Grimes 1 pointed out some important issues regarding cohort studies:
Show More1) The exposure should be clear: we argue to have a clearly defined exposure.
2) The importance of potential confounders: we have been able to include important confounders using the directed acyclic graph, DAG.
3) Awareness that the risk of a weak association (HR 0.5-2) is likely to be due to bias and not causation: We have clearly stated that we have found associations and further that the association could be interesting for further research, but we do not recommend changes in clinical recommendations.
The risks of misclassification of exposure were related to the uterine fibroid diagnoses codes. The daily clinical coding may be incorrect or lacking due to various work-related distractions or variable individual interpretation of clinical cases. The low prevalence of uterine fibroids...
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