Critically Appraise The Article:
Hellevik, A. I., et al. (2017). Age of menarche is associated with knee joint replacement due to primary osteoarthritis (The HUNT Study and the Norwegian Arthroplasty Register). Osteoarthritis and Cartilage 25(10): 1654-1662.
(NOTE: For some of these questions there may not be one “right answer”.)
The following medical background information may help you understand the paper.
Oophorectomy: An oophorectomy is a surgical procedure to remove one or both of the ovaries. Ovaries contain eggs and produce hormones that control menstrual cycle. When an oophorectomy involves removing both ovaries, it’s called bilateral oophorectomy. When the surgery involves removing only one ovary, it’s called unilateral oophorectomy.
Hysterectomy: A hysterectomy is an operation to remove the uterus (womb).
Osteoarthritis: The most common form of joint disease that effects people over the age of 40, resulting in pain and difficulty with activity. There is no treatment so when the disease is very incapacitated, joint replacement surgery is performed. Joint replacement surgery is a marker of severe osteoarthritis.
The Nord-Trøndelag Health Study (HUNT) is Norway’s largest collection of health data about a population. In total 120,000 people from the Nord-Trøndelag county participated. It is a unique database of questionnaire data, clinical measurements and samples from a county’s inhabitants from 1984 onwards. All inhabitants of Nord-Trøndelag county >20 years of age were invited to participate in three surveys: HUNT1 (1984-1986), HUNT2 (1995-1997), and HUNT3 (2006-2008). The studies by Hellevik et al. were carried out using data from the HUNT2 and HUNT3 to examine the association between reproductive history and use of hormonal therapies and the risk of total knee replacement or total hip replacement due to osteoarthritis, the most common form of joint disease that effects people over the age of 40, resulting in pain and difficulty with activity. There is no treatment so when the disease is much incapacitated joint replacement surgery is performed. Joint replacement surgery is a marker of severe osteoarthritis.
1a) Why did the authors conduct this current study? [2 marks]
1b) What are advantages and disadvantages of conducting the current study as part of a large, population-based study designed for multiple purposes?
1c) 35,280 women participated in HUNT2 (75.5% of those invited), and 27,758 women participated in HUNT3 (58.7% of those invited). How would the non-response have affected the results of the study?
1d) What are the advantages and disadvantages of using the HUNT2 and HUNT3 as the study population of the current study?
This current study included 36857 women aged >30 years at baseline, and excluded women with uni/bilateral oophorectomy (removal of one or both ovaries) or hysterectomy (removal of the uterus or womb), with joint replacement before recruitment, with missing date of operation for joint replacement, or with missing data on body mass index/smoking, leaving 30,289 women for the analyses.
2a) What is the reason for excluding the 1183 women with previous joint replacement?
2b) What is the reason for excluding the 3710 women with uni/bilateral oophorectomy or hysterectomy?
2c) “For follow-up, we identified cases with a TKR or THR due to primary osteoarthritis, according to the operating surgeon, using information from the Norwegian Arthroplasty Register (NAR). This linkage was conducted using the 11-digit personal identification number that is unique to each Norwegian citizen. NAR contains a record of over 95% of all TKRs and THRs in Norway”. What are advantages and disadvantages of using NAR to identify the cases with a TKR or THR due to primary osteoarthritis?
3a) What were the exposures studied? How were data on exposures collected?
3b) How valid were the exposure data? Could there have been misclassification of exposure? Please explain.
Table 1 presents various participant characteristics for each category of reproductive and hormonal factors. Table 2 presents participant characteristics at baseline in all women, and those who received a total knee replacement or total hip replacement.
4a) Are there marked differences among women with different levels of reproductive and hormonal factors? Are there marked differences in women who received a total knee replacement or total hip replacement? What are the implications of these differences?
4b) Use the data in Table 2 to calculate the cumulative incidence of total knee replacement and total hip replacement.
4c) In Table 1, it showed that 6253 women has missing data on hard physical activity. How would this affect the results of the study?
Participants were followed up from the date of their baseline data collection. If the participants were followed up until 31 December 2014, how many person-days would be contributed to the follow-up by each of three participants whose baseline data collection took place on April 25, 1995, June 30, 1997, and December 05, 2006, assuming that none of them underwent a joint replacement or died?
In the analyses, what confounders were adjusted for? What other factors do you think that the authors should have considered in examining the association between reproductive history and use of hormonal therapies and the risk of total knee replacement or total hip replacement due to osteoarthritis? [3 marks]
What are the main findings of the article? Comment on these findings. Do you think they are real? What else could the findings be attributed to?
What are the appropriate interpretations of the 95% confidence interval (CI) referred to as ‘statistically significant’ by the authors in the following sentence?
Past users and users of systemic HRT were at higher risk of TKR compared to never users (HR 1.42 (95% CI 1.06 – 1.90) and HR 1.40 (95% CI 1.03 -1.90), respectively).
Cohort studies are considered observational studies, whereas clinical trials are considered experimental studies. Could a randomized controlled trial be conducted to test the hypothesis that use of hormonal therapies may affect the risk of osteoarthritis? Would it provide stronger evidence for a causal relationship? Why or why not? Is this sufficient evidence for causation? Based on this article, would you suggest the use of hormonal therapies in post-menopausal women?