Abstract
Objectives: To evaluate the surgical outcomes of stroke patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP) and compare the clinical outcomes between patients with stroke and those without stroke receiving this procedure.
Methods: This retrospective cohort study analyzed claims data collected during the period of 1997–2012 from Taiwan National Health Insurance Research Database. We enrolled 6625 patients who had persistent lower urinary tract symptoms and underwent TURP for BPH. They were categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient characteristics, postoperative clinical outcomes, medication records, and medical expenses were compared.
Results: Compared with the stroke group patients, those in the nonstroke group were younger, had fewer comorbidities, and more favorable postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8% during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year postoperatively (p = .05). TURP reduced the overall medical expenses of patients with stroke. Annual patient medical expense during 1 year preoperatively, 1 year postoperatively, 2 years postoperatively, and 3 years postoperatively was NT$659,000, NT$646,000, NT$560,000, and NT$599,000, respectively.
Conclusions: In patients with stroke, TURP reduces the risks of UTI and UR and annual total medical expense.
Introduction
Benign prostatic hyperplasia (BPH) affects approximately 210 million men globally and is a major cause of lower urinary tract symptoms (LUTS) in men [Citation1]. An estimated 50% and 75% of men have histologic evidence of BPH by the age of 50 and 80 years, respectively, with approximately 50% of them having clinically considerable symptoms [Citation2]. The treatment of BPH has been a considerable public health challenge, with billions of dollars spent annually for BPH treatment [Citation3,Citation4]. The prevalence of BPH is expected to increase markedly in the near future [Citation5].
Stroke is another threat to the health of elderly men; globally, more than 6 million people experienced first-stroke events in 2010 [Citation6]. Stroke has a serious effect on lower urinary tract function, leading to significant morbidity [Citation7]. Approximately 65% of patients with stroke experience voiding dysfunction during the early stage of stroke [Citation8]. The predominant symptoms of voiding dysfunction are urinary frequency, urinary urgency, and urge incontinence [Citation7]. Moreover, urinary retention (UR) occurs in more than 50% of patients with stroke who have voiding dysfunction [Citation9].
Several complications, such as urinary tract infection (UTI), bladder stones, and renal failure, may occur as a result of recurrent UR [Citation10]. As stroke and BPH have many common risk factors [Citation11] and similar symptoms, such as voiding dysfunction, the management of patients with concomitant BPH/LUTS and stroke is an important issue that cannot be ignored. For most BPH patients with LUTS, alpha blockers demonstrate acceptable safety, efficacy, and outstanding tolerance [Citation12]. However, some patients who do not respond to pharmacological treatment may require endoscopic intervention, such as transurethral resection of the prostate (TURP), which remains the gold standard [Citation13]. Nevertheless, stroke patients receiving TURP have additional anesthetic safety concerns. The benefits of TURP for selected patients with stroke – such as reduced rates of UR and UTI in future and the total annual medical expenses – have not been clarified.
To the best of our knowledge, very few studies have focused on the treatment outcomes of patients with stroke who have undergone TURP. Therefore, in this study, we investigated whether patients with stroke who underwent TURP have reduced rates of infection, UR, reoperation, and postoperative medication dependence as well as total annual medical expenses. For this nationwide observational cohort study, we used the National Health Insurance (NHI) Research Database (NHIRD) of Taiwan to investigate their clinical outcomes.
Materials and methods
Data source
The current study used the Longitudinal Health Insurance Database 2000 (LHID2000), a subset of the NHIRD. The NHIRD contains the claims data from the NHI program of Taiwan, which was established in 1995, and more than 2000 published research articles have used the NHIRD thus far [Citation10]. The LHID2000 includes the claims data of 1,000,000 individuals randomly sampled from all insurants of the NHI program (n = 23.75 million persons) in 2000. We noted no significant difference in demographic characteristics (i.e. gender and region) between the populations derived from the NHIRD and LHID2000.
Study design
We compared treatment outcomes of stroke patients who had undergone TURP with those of controls. Patients with BPH (International Classification of Diseases, Ninth Revision, Clinical Modification code [ICD-9-CM]: 600.xx) who underwent TURP (Taiwan NHI reimbursement procedure codes: 79406B, 79411B, 79412B) between 1 January 1997, and 31 December 2012, a total of 6625 patients were enrolled. Stroke was considered the primary variable of interest. The first TURP was assigned as the index admission if patients underwent repeated TURPs during the study period. For inclusion in our analytic group, we defined patients as having stroke if they had at least one inpatient claims admission record or two outpatient visit claims with a diagnosis of hemorrhagic stroke (ICD-9-CM: 430.xx–432.xx) or ischemic stroke (ICD-9-CM: 433.xx–437.xx) before the index TURP admission. Patients who had any stage of prostate cancer before receiving TURP (ICD-9-CM: 185.xx) were excluded from this study.
Comorbidity detection
We included the following comorbidities: diabetes mellitus (ICD-9-CM: 250.xx), dyslipidemia (ICD-9-CM: 272.4), hypertension (ICD-9-CM: 401.xx–405.xx), Parkinson disease (ICD-9-CM: 332.xx), chronic obstructive pulmonary disease (ICD-9-CM: 491.xx, 492.xx, and 496.xx), ischemic heart disease (ICD-9-CM: 410.xx–414.xx), and heart failure (ICD-9-CM: 428.xx). The presence of a comorbidity was defined when at least one inpatient admission or two outpatient visits for the comorbidity were claimed 1 year before the index date.
Outcome detection
The outcomes examined in our study included rates of UR, UTI, in-hospital deaths, re-TURP, and urological medication dependence after TURP. The total annual medical expenses after TURP were also compared between the two groups. UR was defined as the occurrence of any of the following procedures: intermittent catheterization (Taiwan NHI code: 47013C), Foley catheter indwelling (Taiwan NHI code: 47014C), or cystostomy creation (Taiwan NHI code: 78003C). UTI was defined as admission to the hospital with a UTI-related diagnosis (ICD-9-CM codes: 599.0x and 595.0x) or the occurrence of at least one emergency department or outpatient visit with a diagnosis of UTI and antibiotic prescription. We also analyzed the patients’ BPH symptom-related medication prescription claims for α-blockers, bethanechol, and antimuscarinic agents. Medication prescription was defined as a medication possession ratio (MPR) of more than 50%, implying that the medication was prescribed for 2 weeks in each month.
Statistical analyses
The distribution of the demographic and clinical characteristics of the stroke and nonstroke groups was compared using the chi-squared test for categorical variables and the independent sample t test for continuous variables. The risk of postoperative outcomes was compared between the groups using multivariable logistic regression analysis. The urological medication use of the two groups during 0–3 months and 4–12 months after TURP was also compared using multivariable logistic regression. The medication-free survival rates after TURP were compared between the groups (i.e. stroke vs. nonstroke; ischemic stroke vs. hemorrhage stroke) by using the multivariable Cox proportional hazard model and were depicted as adjusted survival curves for each group. All multivariable analyses, including logistic and Cox regression analyses, were adjusted for the patient’s characteristics and preoperative medication status. The incidence of UTI and UR during 1 year before and after TURP was compared using the McNemar test. Finally, the total annual medical expenses before and after TURP were compared using the Wilcoxon signed-rank test, because of the lack of the normal distribution of expenses. Statistical analysis was conducted using SAS software version 9.4 (SAS Institute, Cary, NC).
Results
Study population
A total of 6625 patients who underwent TURP were included in our study. These patients were categorized into two groups: the nonstroke group (n = 6048; 91%) and stroke group (n = 577; 9%). lists the demographic characteristics, clinical characteristics, and selected comorbidities of the two groups. Patients in the stroke group were older and had higher UTI rates during 3 months preoperatively (27.7% vs. 18.4%, p < .001) and higher UR rates during 3 months preoperatively (47.7% vs. 34.3%, p < .001). Diabetes, dyslipidemia, hypertension, Parkinson disease, chronic obstructive pulmonary disease, ischemic heart disease, and heart failure were more prevalent in the stroke group than in the nonstroke group. A higher amount of prostate tissue was ablated through surgery in the stroke group (p = .003). Stroke group patients were more likely to be prescribed bethanechol before receiving TURP (19.1% vs. 14.3%, p = .002). However, no significant difference was observed in the proportion of patients taking all urologic drugs between the two groups (p = .096).
Table 1. Patient characteristics in nonstroke and stroke groups.
Postoperative adverse events
presents a comparison of the adjusted odds ratios (ORs) between the stroke and nonstroke groups to reveal the associations with postoperative adverse events. The stroke group had a higher risk of UTI (OR, 1.37; 95% confidence interval [CI], 1.13–1.68) and a higher risk of UR requiring catheterization (OR, 1.89; 95% CI, 1.51–2.36) during the period from 1 month to 1 year postoperatively. The stroke group also had a higher risk of in-hospital death than did the nonstroke group (OR, 8.27; 95% CI, 2.47–27.70). Moreover, the life-long re-TURP rates and the time to re-TURP were comparable between the two groups.
Table 2. Clinical postoperative outcomes in nonstroke and stroke groups.
Urologic drug use after TURP
displays the proportions of patients using urologic drugs after TURP. During the first 3 months after TURP, a higher proportion of patients with stroke had taken α-blockers (OR, 1.41; 95% CI, 1.18–1.68). However, borderline significant differences were observed in this proportion between the two groups during 4–12 months postoperatively (p = .071). A higher proportion of patients with stroke had taken bethanechol during 0–3 months postoperatively (OR, 1.39; 95% CI, 1.12–1.74) and 4–12 months postoperatively (OR, 1.55; 95% CI, 1.14–2.11). Finally, considering all urologic drugs, a higher proportion of patients with stroke had taken drugs during 0–3 months postoperatively (OR, 1.43; 95% CI, 1.19–1.72) and 4–12 months postoperatively (OR, 1.27; 95% CI, 1.06–1.52; ).
Figure 1. Risk of urologic drug use in nonstroke and stroke groups during various follow-up periods.
An optimal surgical outcome of TURP is defined as no urological drug use postoperatively. Thus, the adjusted urological medication-free survival rates were compared between the two groups (). Multivariable Cox regression revealed that the stroke group had lower medication-free survival rates during follow-up than did their counterparts (hazard ratio [HR], 1.24; 95% CI, 1.11–1.38; ). In addition, we compared the medication-free survival rates across the different types of stroke (ischemic vs. hemorrhagic), and no difference was observed between these two groups (HR, 0.97; 95% CI, 0.71–1.31; ).
Figure 2. Adjusted medication-free survival curves in nonstroke and stroke groups (A) and hemorrhagic and ischemic stroke groups (B) during follow-up.
UTI and UR before and after TURP
As shown in , from 1 year preoperatively to 1 year postoperatively, the incidence of UTI decreased from 23.6% to 20.3% (p < .001) and from 34.7% to 29.8% (p = .055) in the nonstroke and stroke groups, respectively. Similarly, as shown in , the incidence of UR decreased significantly after TURP in both nonstroke and stroke groups (p < .001).
Figure 3. UTI and UR rates during 1 year before and after TURP in the nonstroke and stroke groups.
Among the stroke subtypes, the incidence of UTI decreased from 34.9% during 1 year preoperatively to 29.3% during 1 year postoperatively in patients with ischemic stroke (p = .038). Similarly, the incidence of UR decreased significantly after TURP in patients with hemorrhagic or ischemic stroke (both p < .001; ).
Figure 4. UTI and UR rates during 1 year before and after TURP in ischemic and hemorrhagic stroke groups.
Medical care expenses
reveals the median total annual medical care expenses of the two groups: From 1 year preoperatively to 2 years postoperatively, the median total annual medical care expenses decreased from NT$659,000 to NT$560,000 (p < .001) and from NT$302,000 to NT$293,000 (p < .001) in the stroke and nonstroke groups, respectively. However, the total annual medical care expenses during 1 year postoperatively were significantly higher than those during 1 year preoperatively only in the nonstroke group (p < .001).
Figure 5. Medical expenses before and after TURP in the nonstroke and stroke groups.
Discussion
The NHIRD comprises anonymous enrollment and eligibility information and claims for outpatient visits, prescribed medications, and procedures of more than 99% of the entire Taiwanese population (estimated at 23 million) [Citation14]. Our study used the LHID2000, which contains all inpatient and outpatient medical claims of 1 million beneficiaries randomly sampled from the NHIRD during the period from 1 January 1997 to 31 December 2012. Consequently, the patients’ characteristics were assumed to be similar to those of the whole population.
TURP is currently the gold standard for BPH treatment [Citation15]. Although the overall complication rates have been decreasing, only 8–10% of patients have undergone the procedure thus far [Citation16]. The possible postoperative complications include bleeding, clot retention, bladder wall injury, TURP syndrome, UTI, UR, urinary incontinence, urethral stricture, and retrograde ejaculation [Citation15]. Moreover, operating on patients with a stroke history is a challenge for surgeons. Surgery on these patients is associated with more anesthetic safety concerns, longer hospital stay, higher healthcare resource utilization, and higher perioperative mortality than that on patients without stroke [Citation17]. In our study, the stroke group accounted for only approximately 9% of the whole study population, and the preoperative comorbidities of diabetes, dyslipidemia, hypertension, Parkinson disease, ischemic heart disease, and heart failure were more prevalent in the stroke group than in the nonstroke group. Moreover, a higher amount of prostate tissue was ablated through surgery in the stroke group, which is one of the factors influencing morbidity in patients undergoing TURP [Citation18].
Neurogenic bladder is also a sequela of patients with stroke and may cause the surgeon to be hesitant to perform TURP on patients with stroke. Urinary incontinence can affect 40–60% of people admitted to a hospital after a stroke, with 15% remaining incontinent after 1 year [Citation19]. UR also occurs in approximately 29% of patients with stroke [Citation20]. Urodynamic evaluation of patients with LUTS following stroke revealed that 35% of men had concomitant bladder outlet obstruction [Citation21]. Another study also revealed that among patients with ischemic stroke, 70.3% and 29.3% had detrusor overactivity and underactivity, respectively [Citation22]. Voiding dysfunction is noted in patients with stroke because of mechanical obstruction caused by prostate tissue as well as interruption of the neuromicturition pathways, leading to poststroke detrusor overactivity or underactivity [Citation23]. Consequently, the treatment outcomes of TURP for patients with a stroke history are difficult to predict preoperatively.
Our study is valid and practical because it reveals the treatment outcomes of TURP for patients with a stroke history through the analysis of a large population-based database. The stroke group had a higher risk of in-hospital death than did the nonstroke group. It also had higher risks of UTI and UR requiring catheterization during the period from 1 month postoperatively to 1 year postoperatively. Compared with the controls, patients with a stroke history had higher rates for continuing medication after TURP; these findings demonstrate that they had worse surgical outcomes. However, the longitudinal observation focusing on the stroke group showed that these patients benefitted from receiving the procedure, because TURP reduced their incidence of both UTI and UR. TURP could also reduce the total annual medical care expenses; this phenomenon was not remarkably observed in the nonstroke group. The medical care expenses of patients with stroke are extremely high. In the United States, the medical care expenses of patients with stroke were estimated to be approximately US$65.5 billion in 2010 [Citation24]. In Europe, the annual medical care expenses of these patients were approximately €64.1 billion in 2010 [Citation25]. In Taiwan, the mean total annual medical cost per stroke patient was approximately US$5900, and symptomatic UTI was one of the significant predictors for these increasing expenses [Citation26]. Our study speculates that TURP improves the quality of voiding of patients with stroke, which reduces the frequency of urological intervention and the risks of UTI and UR, consequently reducing the total annual medical care expenses.
This study has limitations attributable to the data structure of the NHIRD. First, the diagnoses of comorbidities were dependent on the ICD-9-CM. Therefore, we defined a stroke diagnosis as at least two outpatient visits or 1 hospitalization admission, which have already been validated. This method ensured that patient selection was more reliable and precise. Second, there are many important laboratory parameters which have been proven to impact male LUTS in the literature, for example, prostate specific antigen (PSA) [Citation27], glycemic level [Citation28], and testosterone level [Citation29]. The NHIRD does not contain these confounding variables which may impact our study results. We also could not assess whether the time from stroke to surgery affects the treatment outcome of TURP by using this database. Third, apart from alpha blockers, there were many newly-developed drugs coming out in succession during our study period, like daily used phosphodiesterase type 5 (PDE-5) inhibitors [Citation30] and 5-alpha reductase inhibitors (5-ARI) [Citation31]. The consumptions of PDE-5 inhibitors and 5-ARI were not included in the calculation for medication-free survivals, which may cause some bias in our study. Meanwhile, new generation of minimally invasive surgery like prostatic vaporization and ablation through laser [Citation32], or prostatic thermos-balancing technique [Citation33], were not reimbursed in the NHI program, either. Although our study has limitations attributable to the data structure of the NHIRD, we believe that this study is innovative and effective, because to the best of our knowledge, this is the first study to discuss the surgical outcomes of patients with stroke who had undergone TURP. The treatment outcomes of the stroke group were poor compared with those of the non-stroke group; nevertheless, patients with stroke may benefit from receiving this surgical procedure.
Conclusions
This population-based observational study revealed that patients with stroke had a higher incidence of UTI and UR after TURP. Patients with stroke also had higher rates of continuing medication after TURP. These findings indicated that they had relatively poor treatment outcomes compared with those of patients without stroke. Nevertheless, according to our longitudinal observation of the stroke group, patients benefitted from receiving TURP, because this procedure reduced their risk of future voiding complications and total medical expenses. Additional large-scale randomized clinical trials and well-designed basic research are needed before definite conclusions can be drawn.
Acknowledgements
This work was supported by Chang Gung Memorial Hospital (Grant numbers: CMRPG3C0441/CMRPG3E0151-3) and the National Science Council, Taiwan (NSC 104-2314-B-182A-140-MY3).
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
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