ORIGINAL RESEARCH |
https://doi.org/10.5005/jp-journals-10002-1457 |
Long-term Survival Following Parathyroidectomy for Primary Hyperparathyroidism in Elderly People with Polypharmacy
1Department of Public Health, La Trobe University, Bundoora, Victoria, Australia
Corresponding Author: Shaun F Purkiss, Department of Public Health, La Trobe University, Bundoora, Victoria, Australia, Phone: +617455840374, e-mail: purkisss@googlemail.com
Received on: 23 September 2021; Accepted on: 12 September 2023; Published on: 30 October 2023
ABSTRACT
Aim: Primary hyperparathyroidism (PHP) is associated with many chronic conditions. Polypharmacy may, therefore, be a feature of those people with PHP considered for parathyroidectomy. This study examines the medication profile of elderly people undergoing parathyroidectomy for PHP and the association of polypharmacy with long-term survival.
Materials and methods: A publicly available Australian administrative data source describing medical services and pharmacy dispensing between 2003 and 2015 was used. Persons undergoing parathyroidectomy for PHP aged >60 years were identified from procedure codes and their dispensing profile was examined in the year prior to surgery. Polypharmacy was defined as taking more than five concomitant medications. Survival following parathyroidectomy was assessed in relation to age and polypharmacy groupings.
Results: A total of 608 persons (461:147, F:M) undergoing parathyroidectomy for PHP (mean age 72.1 years) were recruited. The prevalence of polypharmacy in parathyroidectomy-treated persons was 42%. Polypharmacy prevalence and cardiovascular treatment prevalence increased with age but were lower than control groups.
Overall, 5-year survival following parathyroidectomy for PHP was 91% (controls 88%, log-rank 0.01) and was influenced by the level of polypharmacy in all groups. The elderly aged >75 years with polypharmacy had better survival following parathyroidectomy than controls (5-year survival 0.90 vs 0.77, log-rank 0.002).
Conclusion: The prevalence of polypharmacy and cardiovascular treatments in this elderly Australian cohort undergoing parathyroidectomy for PHP is lower than controls. The long-term survival of those aged >75 with polypharmacy is better than age-matched controls. It is likely that patients undergoing parathyroidectomy for PHP are a highly selected group.
Clinical significance: Administrative data can provide a perspective of people undergoing parathyroidectomy for PHP and examine survival outcomes. Presently, Australian surgeons are rigorous in the selection of elderly patients undergoing surgery such that long-term survival outcomes appear better than those observed in control populations.
How to cite this article: Purkiss SF. Long-term Survival Following Parathyroidectomy for Primary Hyperparathyroidism in Elderly People with Polypharmacy. World J Endoc Surg 2023;15(2):29–33.
Source of support: Nil
Conflict of interest: None
Keywords: Administrative data, Australia, Parathyroidectomy, Parathyroids, Polypharmacy, Primary hyperparathyroidism
INTRODUCTION
Polypharmacy, defined as taking at least five prescribed medications, is often connected with the coexistence of many health problems.1-3 Primary hyperparathyroidism (PHP) is associated with a variety of chronic diseases that may include hypertension, gastroesophageal reflux disease, and psychological disorders.4,5 These conditions often require drug treatment. Accordingly, if there is multiple morbidity in people with PHP, then there is the likelihood of concomitant polypharmacy.
Parathyroidectomy is an established treatment for PHP, and some of these associated conditions may improve following surgery.5,6 However, many chronic diseases associated with PHP will require continuous drug treatment for the rest of life.6
Primary hyperparathyroidism (PHP) predominantly affects people aged >60 years, and with increasing age, people will likely develop multiple chronic diseases requiring numerous medications.4-8 Therefore, multiple morbidity and polypharmacy may be a feature of PHP and the age of those people considered for surgery.2,3,9
These factors may influence the decision to operate on elderly people with PHP. Parathyroidectomy is considered a safe procedure in elderly persons with PHP.10 However, some commentators have advised that both polypharmacy and frailty should be factors used to individualize surgical decisions.11 While others have indicated that parathyroidectomy is underutilized in elderly people with PHP.4
This study examines the association of long-term survival with preoperative levels of polypharmacy in people undergoing parathyroidectomy for PHP. The analysis uses a publicly available Australian Ministry of Health data source that records items of service and the dispensing of drugs for the period 2003–2015.
MATERIALS AND METHODS
Study Design
This study was of quasi-longitudinal design and used administrative pharmaceutical and service provision data from Australia. Participants undergoing parathyroidectomy for PHP were identified and assessed for the influence of age and the levels of polypharmacy on long-term mortality rates.
Data Sources
A sample of the Australian Pharmaceutical Benefits Scheme (PBS) and Medicare Benefits Schedule (MBS) datasets were used for this study.2 The datasets contain details of the historical medical and pharmaceutical services rendered to 2.2 million Australians, a random 10% sample of the population. These data were made available by the Australian Department of Health and contained deidentified person-level data that covers the period 2003–2015. Authorization for the study was obtained through the La Trobe University Ethics Committee (approval number S17-177).
Participants
Persons undergoing parathyroidectomy for PHP were identified using MBS procedure codes. Subgroups were defined with three levels of polypharmacy, which included nonpolypharmacy (zero to four drugs), polypharmacy (five to nine drugs), and hyperpolypharmacy (10 or more drugs).2 The definitions comprised drugs with distinct anatomical therapeutic chemical (ATC) subclasses that were dispensed for at least 28 days within the year prior to surgery and excluded food supplements and alternative medications.1,2 An age and gender-matched control population for comparison with treated groups was also recruited from the PBS dataset.
Mortality
The date of the last service provision or prescription exchange recorded within the MBS or PBS data was used as a proxy event marker for mortality. The survival time was calculated for individual persons from the date of parathyroid surgery to the last MBS or PBS signal within the data. In survival modeling, the event was censored if the last service provision was within the last year of the dataset. This allowed for an adequate period between the date of cessation of service and the end of the dataset to consider the event significant.
Statistical Analysis
Kaplan–Meier modeling was used for representing the time of the cessation of service events, the proxy mortality marker. Analysis was performed in Statistical Package for the Social Sciences (SPSS) (version 25; IBM SPSS Statistics, Armonk, New York, United States of America). Comparisons of survival rates between people undergoing parathyroidectomy and controls were made using log-rank tests. Comparison of proportions used Chi-squared tests, and statistical significance was set at p < 0.05. The construction of this manuscript followed the guidelines recommended in the reporting of studies conducted using observational routinely collected health data statements.12
RESULTS
The number of participants in the control and parathyroidectomy groups recruited into this study is shown in Table 1. The mean age of all individuals undergoing parathyroidectomy for PHP was 72.1 years [standard deviation (SD) 7.0]. There were no differences in age between males and females, and with the control group, the mean age was 71.4 years (SD 8.1).
| Age and gender groups | Control n (%) | Parathyroidectomy n (%) | Total |
|---|---|---|---|
| Group I: age 60–65 years | 537 (24) | 87 (14) | 624 |
| Female | 289 (13) | 67 (11) | 356 |
| Male | 248 (11) | 20 (3) | 268 |
| Group II: age 65–75 years | 924 (42) | 310 (51) | 1,234 |
| Female | 454 (21) | 232 (38) | 686 |
| Male | 470 (21) | 78 (13) | 548 |
| Group III: age >75 years | 736 (34) | 211 (35) | 947 |
| Female | 451 (21) | 162 (27) | 613 |
| Male | 285 (13) | 49 (8) | 334 |
| Total | 2197 | 608 | 2,805 |
Polypharmacy
The number of different medications supplied to people undergoing parathyroidectomy (median, range) was four (0, 16) medications. This was lower than the PBS control group, which had a median of five (0, 18) medications (p < 0.001). The extent and frequency of polypharmacy dispensed to these two groups are compared in Figure 1.
Fig. 1: The number of distinct medications dispensed between people undergoing parathyroidectomy for PHP and controls in a calendar year
The prevalence of polypharmacy (more than five medications) in treated people prior to parathyroidectomy was 18% in persons aged 60–64 years of age, 36% in persons aged 65–74, and 62% in persons aged >75. These were all significantly less than values in age-matched controls (37, 53, and 76%).
The most common ATC-defined therapeutic subgroups dispensed were cardiovascular treatments, with 67% of persons undergoing parathyroidectomy receiving these medications. Of these, 25% were dispensed one cardiovascular treatment, and 23, 10, 6, and 2% of persons were dispensed between two and five medications, respectively, from other distinct ATC-defined cardiovascular subgroups.
Treatments were dispensed to 44% for acid disorders, 40% for the control of pain, 23% for glaucoma and psychological conditions, 20% for bone conditions, and 10% for diabetes. There was a wide range of polypharmacy patterns dispensed to people undergoing parathyroidectomy, with 62% of people having an individual configuration of allotted treatments. Around 7% had no treatments dispensed. The most frequent combinations of treatments dispensed to persons undergoing parathyroidectomy are shown in Table 2.
| Combinations of dispensed ATC-defined treatments | Frequency (%) |
|---|---|
| Cardiovascular—dyslipidemia | 39 |
| Antacids—blood—cardiovascular | 19 |
| Antacids—glaucoma | 13 |
| Antacids—cardiovascular | 13 |
| Antacids—dyslipidemia | 13 |
| Antacids—respiratory | 12 |
| Dyslipidemia—respiratory | 11 |
| Antacids—bone | 11 |
| Bone—pain | 10 |
| Antacids—blood—cardiovascular—dyslipidemia | 9 |
| Antacids—cardiovascular—dyslipidemia | 8 |
| Cardiovascular—glaucoma | 7 |
| Cardiovascular—respiratory | 4 |
| Antacids—rheumatological—pain | 3 |
The prevalence of dispensed cardiovascular treatments was lower in persons undergoing parathyroidectomy for PHP as compared to age and sex-matched controls (Fig. 2) (p < 0.02). The prevalence of dispensed diabetes medications was also lower in patients submitted to parathyroid surgery (10%) compared to controls (16%, p < 0.001).
Fig. 2: The prevalence of cardiovascular disease in parathyroidectomy-treated persons compared to age-matched controls (all comparisons p < 0.02)
Survival
The 5-year survival [standard error (SE)] of people aged >60 years undergoing parathyroidectomies for PHP was 0.91 (0.02). This was better than the age and gender-matched control population [0.88, (0.01) log-rank = 0.01] (Fig. 3). Increasing age and the level of polypharmacy were shown to influence survival (Table 3).
| Age-group | Polypharmacy group | Control | SE | Parathyroidectomy | SE | Significance |
|---|---|---|---|---|---|---|
| Aged 60–64 | All | 0.98 | 0.01 | 0.91 | 0.02 | ns |
| I | 0.98 | 0.01 | 0.98 | 0.01 | NS | |
| II | 0.98 | 0.01 | 0.79 | 0.14 | 0.003 | |
| III | 0.96 | 0.03 | 0.86 | 0.14 | NS | |
| Aged 65–74 | All | 0.94 | 0.01 | 0.96 | 0.02 | NS |
| I | 0.96 | 0.01 | 0.97 | 0.01 | NS | |
| II | 0.92 | 0.02 | 0.88 | 0.09 | NS | |
| III | 0.90 | 0.03 | 0.75 | 0.22 | NS | |
| Aged >74 | All | 0.74 | 0.02 | 0.82 | 0.05 | 0.004 |
| I | 0.79 | 0.04 | 0.80 | 0.09 | NS | |
| II | 0.77 | 0.03 | 0.90 | 0.04 | 0.002 | |
| III | 0.62 | 0.04 | 0.77 | 0.06 | 0.005 |
Fig. 3: Survival of persons undergoing parathyroidectomy aged >60 years with PHP and matched controls (log-rank <0.02)
There was a general tendency for the most elderly cohorts undergoing parathyroidectomy to have better survival than control groups. Figure 4 shows this difference and compares persons aged >75 years undergoing parathyroidectomy with polypharmacy and hyper-polypharmacy as compared to controls matched by age and the level of polypharmacy (Log-rank <0.02).
Fig. 4: Survival of persons undergoing parathyroidectomy aged >70 with polypharmacy for PHP and matched controls (log-rank <0.02)
DISCUSSION
This study examined 608 people over 60 years with PHP who underwent parathyroidectomy between 2003 and 2014. It measured the long-term survival of individuals following surgery and compared three groups based on the level of polypharmacy at the time of surgery. Survivals were assessed in comparison to age and sex-matched PBS-derived controls.
The prevalence of polypharmacy, cardiovascular conditions, and diabetes were significantly lower in people undergoing parathyroidectomy as compared to age-matched controls. The degree of polypharmacy negatively influenced long-term survival in people with PHP undergoing parathyroidectomy and control groups. The long-term survival of parathyroidectomy-treated individuals was better than control groups, irrespective of the levels of polypharmacy. Persons aged >70 years undergoing parathyroidectomy with polypharmacy were noted to have the largest differences in survival when compared to controls.
The mortality risk of people with PHP is generally considered higher when compared to the general population, and parathyroidectomy has been considered to lower this risk.13-15 It is likely that this mortality risk is not completely reversed, and survival following parathyroidectomy may be related to several preoperative factors.16,17
Long-term survival following parathyroidectomy has been shown to be broadly similar in men and women.17 However, a high preoperative calcium level has been associated with poorer survival in parathyroidectomy-treated groups.13,17 Clifton-Bligh et al. were not able to confirm this in an Australian cohort but noticed poorer survivals in people with preoperative evidence of diabetes or cardiovascular disease.15
Polypharmacy is recognized as associated with frailty in older people and consequently has an increased risk of complications, reoperation, and prolonged durations of hospital stay after surgical procedures.3,7 Seib et al. commented that patient frailty should be used to individualize treatment in people with hyperparathyroidism.4 It is reasonable, therefore, that surgeons are cautious in offering surgery to the more elderly age-groups, especially those with polypharmacy. However, as noted by Seib et al., the selection may be too rigorous, and the process might act as a barrier to effective treatment.11
Nonsurgical options, such as the use of calcimimetic agents that increase the sensitivity of the calcium-sensing receptors, may be appropriate therapeutic options for PHP in the elderly.18 However, surgeons can be reassured that parathyroidectomy is safe with lower mortality and morbidity rates when compared to elective hernia repair in all age-groups, including those aged >80 years of age.10
Clinical Significance
This study identified polypharmacy as a determinant of long-term survival following parathyroidectomy for PHP. Australian surgeons are likely exercising rigorous case selection and choosing the healthiest people with PHP suitable for parathyroidectomy as the prevalence of polypharmacy, diabetes, and cardiovascular disease is lower in parathyroidectomy-treated groups. This may account for the better long-term survivals observed in most elderly people with polypharmacy undergoing parathyroidectomy compared to age-matched controls.
ORCID
Shaun F Purkiss https://orcid.org/0000-0002-5596-5462
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