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Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards
European Journal of Internal Medicine xxx (xxxx) xxx–xxx
Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original Article
Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards ⁎
Nicole Corsia, , Anna Robertoa, Laura Cortesib, Alessandro Nobilib, Pier Mannuccio Mannuccic, Oscar Corlia, REPOSI Investigators1 a
Pain and Palliative Care Research Unit, Oncology Department, IRCCS-Mario Negri Institute for Pharmacological Research, Milan, Italy Quality Assessment of Geriatric Therapies and Services Laboratory, Neuroscience Department, IRCCS-Mario Negri Institute for Pharmacological Research, Milan, Italy c Scientific Direction, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy b
A R T I C LE I N FO
A B S T R A C T
Keywords: Aging Chronic pain Undertreatment Analgesic treatment Pain management
Background: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic. Objective: We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards. Methods: Taking advantage of the “REgistro POliterapie Società Italiana Medicina Interna” (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old. Among them, 582 patients were affected by pain (either chronic or acute) and 296 were diagnosed with chronic pain. Results: Patients with pain showed worse cognitive status, higher depression and comorbidities, and a longer duration of hospital stay compared to those without pain (all p < .0366). Patients with chronic pain revealed lower level of independency in their daily life, worse cognitive status and higher level of depression compared to acute pain patients (all p < .0156). Moreover, most of them were not treated for pain at admission (73.4%) and half of them was not treated with any analgesic drug at discharge (50.5%). This difference affected also the reported levels of pain intensity. Patients who received analgesics at both admission and discharge remained stable (p = .172). Conversely, those not treated at admission who received an analgesic treatment during the hospital stay decreased their perceived pain (p < .0001). Conclusions: Our results show the need to focus more attention on the pharmacological treatment of chronic pain, especially in hospitalized elderly patients, in order to support them and facilitate their daily life after hospital discharge.
1. Introduction The elderly population is progressively increasing worldwide and chronic pain represents a characteristic among 66% of people aged over 65 years old [1]. Women are generally more likely affected by chronic pain than men [1–3]. Management of chronic pain in the elderly is still challenging, due to several age-related physiological changes causing pharmacokinetic and pharmakodynamic issues [4], and to the wide spectrum of primary diseases and comorbidities that usually include such chronic conditions as impaired sensory and cognitive capacities, abnormal kidney and cardiovascular functioning [5–7], diabetes mellitus, hypertension [8], depression, hip fracture, stroke, colorectal and lung cancer [9]. Among the risk factors affecting mortality, comorbidities are considered equally important as the main disease, being
⁎
1
present in approximately 89% of the discharged patients and in approximately 97% of those who died during the hospital stay [8]. Many of these comorbidities are themselves causes of pain. There is a wide agreement on the multidisciplinary approach necessary to assess and relieve pain in the elderly [10–14], since its inadequate recognition and treatment lead to a high probability of adverse negative outcomes such as functional impairment, falls, slower rehabilitation, mood alterations (e.g. depression and anxiety), reduction of socialization, deterioration of nutritional status, sleep disorders and overall a reduced quality of life [15,16]. Generally, from a pharmacological perspective, opioids are considered as the most powerful painkillers. An Italian study [17] based on the “REgistro POliterapie Società Italiana Medicina Interna” (REPOSI) showed that patients with chronic pain were prescribed with a rate of opioids prescription that increased from 3.8% to 5.8% when
Corresponding author at: Pain and Palliative Care Research Unit, Oncology Department, IRCCS Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, Milan, Italy. E-mail address: [email protected] (N. Corsi). Please, refer to the Supplementary Data, Appendix.
https://doi.org/10.1016/j.ejim.2018.05.031 Received 16 February 2018; Received in revised form 10 May 2018; Accepted 23 May 2018 0953-6205/ © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Nicole, C., European Journal of Internal Medicine (2018), https://doi.org/10.1016/j.ejim.2018.05.031
European Journal of Internal Medicine xxx (xxxx) xxx–xxx
N. Corsi et al.
comparing admission with discharge. Moreover, more than 50% of patients were administered with five or more different drugs, highlighting that the prescription of opioids is often associated with polypharmacy. These co-treatments may induce new clinical issues due to drug-to-drug interactions or drug-related adverse events. For instance, sedation and respiratory depression might occur when opioids are administered together with anticonvulsants, benzodiazepines, antipsychotics, selective serotonin reuptake inhibitors and antidepressants. These interactions highlight a potential relation between opioid-related mortality and medicines commonly used for chronic pain [18]. Considering the need to increase knowledge on pain in the hospitalized elderly, we chose to analyze the data from REPOSI with the goal to investigate pain prevalence and intensity, and its pharmacological management in elderly patients hospitalized in internal medicine and geriatric wards, with a special focus on the subset of those with chronic pain.
classifications are described elsewhere [19]. The pharmacological therapy was encoded according to the Anatomical Therapeutic Chemical (ATC) classification system and gathered into different categories of prescribed drugs: nonsteroidal anti-inflammatory drugs (NSAIDs, such as aspirin, ibuprofen, ketorolac, ketoprofen, COX2-inhibitors), paracetamol, opioids (WHO step 2, weak opioids such as codeine and tramadol; WHO step 3, strong opioids such as morphine, hydromorphone, methadone, fentanyl, oxycodone) adjuvant analgesics (such as tricyclic antidepressants, anticonvulsants, corticosteroids, bisphosphonates). The nature of pain (acute vs. chronic) was first assessed by the physician and then patients were asked to rate the level of perceived pain on a numeric rating scale (NRS), ranging from 0 (no pain) to 10 (the worst imaginable pain).
2. Materials and methods
Characteristics of patients with or without pain, and those with acute or chronic pain were compared using univariate analysis by means of chi-squared tests for categorical variables, and t-tests or analysis of variance (ANOVA) for continuous variables. The odds ratio (ORs) for patients administered with analgesic treatment compared to those not treated were analyzed using logistic regression models adjusting for age, sex, type of pain, functional and cognitive status, and depression. Analyses were performed using JMP Pro 13 (SAS Institute Inc. Cary. NC. USA) and Stata 13.0 (Stata Corp LP, College Station, Texas, USA). P-values < .05 were considered statistically significant.
2.2. Statistical analysis
From January 2012 to December 2014, 101 centers (86 from Italy and 15 from Spain) participated in the REPOSI register, a collaborative network between the Italian Society of Internal Medicine (SIMI, Societa` Italiana di Medicina Interna), the IRCCS Mario Negri Institute of Pharmacological Research and the IRCCS Ca′ Granda Maggiore Policlinico Hospital Foundation. The design of REPOSI was previously described [19]. This network aims to assess the prevalence of multiple diseases and pharmacological treatments of elderly people hospitalized in internal medicine wards in order to describe the relation between the clinical characteristics of the patients and the appropriateness of prescribed drugs. Additionally, it aims to evaluate the clinical status and drug prescription at admission, discharge and 3-month follow-up, the latter being verified by phone calls. The REPOSI network enrolled patients consecutively admitted to the participating hospital wards during a period of 4 weeks, 3 months apart from each other (in February, June, September, December 2012 and 2014). Inclusion criteria were age ≥ 65 years old and acceptance to sign the informed consent. Exclusion criteria included seriousness of patient's clinical condition and admission in terminal state. Participants signed the informed consent approved by the ethics committee of the IRCCS Ca′ Granda Maggiore Policlinico Hospital Foundation, Milan. 2535 patients were enrolled (2366 Italian and 169 Spanish). Among them, 5 were excluded because of missing information on the main outcome (pain), and 19 because they had post-operative pain, that is different in nature and treatment compared to chronic pain. Table 1 shows the social, educational, and clinical characteristics of the examined sample, distinguishing the general participants from those with pain, acute or chronic. Additionally, with the goal to evaluate the evolution of chronic pain from admission to discharge, we further excluded 63 patients because death occurred during hospitalization, transfer or missing data, and 124 patients who reported pain at admission but not at discharge. All the collected data were monitored by a central institution (Mario Negri Institute) for consistency, accuracy (with contacts of the peripheral clinical centers if necessary) and statistical analysis.
3. Results Results showed that among 2511 patients eligible for the analysis, 659 suffered from pain and 1852 did not (see the flow-chart, Fig.1). Among those with pain, 54.2% were women and pain patients differed from those without pain for living arrangements (p < .0001) and sex distribution (p = .0061). Patients suffering from pain showed worse cognitive status (p = .0366), higher levels of depression (p = .0004) and number of comorbidities (p = .0004), and a longer duration of hospital stay (p = .0026) compared to those who did not report pain (Table 1). Among 582 patients with pain, those with acute pain were comparable in number to those with chronic pain (286 and 296, respectively). There were lower level of independency in the activities of daily life (p < .0001), worse cognitive status (p = .0156) and higher level of depression (p = .0112) in the chronic pain compared with the acute pain population (Table 1). The multivariate analysis to check any possible influencing role of geriatric assessment variables in the administration of analgesic treatment showed that the worse the cognitive status, the lower the probability to be administered with WHO2 opioids (p = .005), and that the better the functional status, the higher the probability to be administered with WHO3 opioids (p = .020). However, no additional significances were found (Supplementary Data, Supplementary Table). By focusing on chronic pain patients who reported pain at both admission and discharge (N = 109), most of them were not treated for pain at the time of admission (73.4%). The remaining patients were already treated at admission with one analgesic drug (i.e. monotherapy, 22%) or with two or more drugs (i.e. polytherapy, 4.6%). At discharge, half of the chronic pain patients received no analgesic prescription (50.5%), the other half received a monotherapy (33.9%) or polytherapy (14.7%) analgesic prescription. By analyzing the type of analgesics, most chronic pain patients were treated with WHO-step 3 drug at admission (11.9%) but with WHO-step 2 during the hospital stay (19.2%) and at discharge (17.6%) (Fig.2). Our analysis on pain intensity showed a slight decrease in pain reports comparing admission (NRS pain average 4.9) with discharge (NRS pain average 4.7), although the difference was not statistically significant (p = .1532). Those patients who received an analgesic
2.1. Data collection All data obtained during the visits were entered into a standardized web-based case report form by the physician who attended the assessment. All the personnel involved in data collection was trained prior to the starting date in order to standardize the procedure of patient inclusion and evaluation. The following data were recorded for each patient: socio-demographic characteristics, body mass index, risk factors, severity and comorbidity index, cognitive functioning assessment, duration of hospital stay, state of patients at discharge and pharmacological therapy. Moreover, we recorded both the intensity and nature (acute vs. chronic) of pain. The evaluating tools and diagnosis 2
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Table 1 - Sample descriptive characteristics.
Age (mean ± SD) Age classes (N, %) 65–74 75–84 ≥ 85 Education (years) (mean ± SD) Marital status (N, %) Single Married Widow/er Living arrangement (N, %) Alone With spouse With sons With spouse and sons Other BMI (mean ± SD) SI at admission (mean ± SD) CI at admission (mean ± SD) BI at admission (mean ± SD) SBT (mean ± SD) GDS (mean ± SD) Duration of hospital stay. (mean ± SD) State of the patients at discharge (N, %) Discharge Discharge Critical condition Transferred Dead Total number of drugs (mean ± SD) GFR [20] (mean ± SD)
General population
Pain population
N = 1852
N = 659
79.3 ± 7.6
78.9 ± 7.1
541 800 509 6.2 ± 4.6
29.2 43.2 27.5
157 1006 613 346 836 255 106 145 25.9 ± 5.0 1.6 ± 0.3 3.0 ± 1.9 78.0 ± 30.1
Chronic pain population
Acute pain population
N = 296
N = 286
0.3115
79.1 ± 7.2
78.7 ± 7.2
0.3380
91 131 74 5.9 ± 4.5
30.7 44.3 25
198 299 162 6.2 ± 4.6
30.0 45.4 24.6
8.5 54.7 33.3
69 320 241
10.5 48.8 36.7
0.1721
31 140 114
19.6 47.4 14.5 6 8.2
184 266 96 37 41 25.9 ± 5.2 1.7 ± 0.4 3.4 ± 2.0 80.0 ± 26.4
28.8 41.7 15.0 5.8 6.4
< 0.0001
0.9085 < 0.0001 < 0.0001 0.1073
75 120 47 18 21 26.2 ± 5.8 1.8 ± 0.3 3.5 ± 2.0 75.4 ± 28.6
0.0366 0.0004 0.0026
9.1 ± 2 1.6 ± 1.3 13.4 ± 12.2
0.1425
248 3 30 15 6.5 ± 3.45 61.1 ± 25.4
9.0 ± 8.1 1.2 ± 1.3 11.6 ± 9.4 1623 16 131 79 5.5 ± 3.1 59.4 ± 24.2
p
0.7018
8.3 ± 7.1 1.4 ± 1.3 12.9 ± 10.5 87.8 0.9 7.1 4.3
558 6 65 30 5.9 ± 3.4 60.1 ± 24.0
84.7 0.9 9.9 4.5
0.0115 0.5189
p
0.5833
81 134 71 6.2 ± 4.5
28.3 46.8 24.8
10.5 47.5 38.6
31 142 97
10.9 50.0 34.1
0.4830
26 41.7 16.3 6.2 7.3
84 120 38 15 15 25.6 ± 4.4 1.7 ± 0.4 3.3 ± 2.0 84.5 ± 23.7
30.1 43.1 13.6 5.4 5.4
0.7624
0.5677
0.1954 0.0214 0.0966 < 0.0001
7.6 ± 6.9 1.3 ± 1.2 12.5 ± 8.8 83.8 1 10.1 5.1
250 3 25 8 5.5 ± 3.2 59.5 ± 22.0
0.7766
0.0156 0.0112 0.3241 83.8 1.0 8.7 2.8
0.4896
0.0002 0.4056
Abbreviations: BMI = body mass index; SI = severity index; CI = comorbidity index; BI = Barthel index; SBT = short blessed test; GDS = geriatric depression scale; GFR = glomerular filtration rate.
the time of admission. Thus, undertreatment is related to the choice of previous physicians (e.g. family practitioners) rather than internal medicine physicians. However the data recorded at hospital discharge showed that 50.5% of patients that reported chronic pain still remained untreated, thus extending the concern for undertreatment also to the hospital stay and physicians. A second observation regards the choice of the administered analgesics. At admission, patients with chronic pain were treated with one (i.e. monotherapy, 22%) or more (i.e polytherapy, 4.6%) analgesic drugs. During the hospital stay, physician did apparently modify the pharmacological approach in order to better manage patients' pain, so that at discharge 48.6% of patients were treated with monotherapy (33.9%) or polytherapy (14.7%). Regarding the type of analgesic, all the medications of the classes (NSAIDs, paracetamol, opioids and adjuvants) were administered to a greater extent at the time of discharge than at admission. The increasing administration of NSAIDs, almost doubled at the time of discharge, is of concern because their use needs caution due to the high risk of adverse effects in the elderly [14]. At the same time, paracetamol, despite being considered as a safe drug in the elderly, was less prescribed at the time of discharge. A third observation regards the questionable efficacy of the administered pain medications. Results showed that the average pain intensity reported by the chronic pain patient population decreased from 4.9 to 4.7 out of 10 comparing admission to discharge. By separately analyzing pain intensity of treated vs. untreated patients at both admission and discharge, it turned out that the former rated their pain intensity 4 of 10 points, while the latter scored about 5 of 10 points at both admission and discharge. The difference between pain ratings of treated and untreated patients is clinically quite unsatisfactory. According to the Farrar criteria, a good response to analgesics should be reflected in a difference in pain intensity before and after treatment. A
treatment at both admission and discharge (N = 26) remained stable (4.0 ± 2.4 vs. 4.3 ± 2.0, respectively; p = .172). Conversely, those not treated at admission but who received analgesics during the hospital stay (N = 27) decreased significantly the perceived level of pain (5.0 ± 2.3 vs. 4.1 ± 2.0; p < .0001) (Table 2). 4. Discussion Our goal was to analyze prevalence, nature and severity of pain, and its pharmacological treatment in elderly patients hospitalized in internal medicine wards. In our sample, 582 of 2511 patients (23.2%) experienced pain. Among them, 296 (i.e., 11.8% of the whole sample) had chronic pain. This rate, much lower than usually reported, is more likely to represent an underestimation in the diagnosis of pain rather than an effectively less painful population. The presence of pain was associated with worse severity and comorbidity index, cognitive and depressive status, and number of administered drugs at admission. Furthermore, the presence of pain led to a longer hospital stay. By comparing chronic with acute pain patients, we found that autonomy level, depressive status and cognitive functions were worse in chronic pain patients. This decline of cognitive functions is in accordance with previous findings [21–24], considering that pain itself contributes to worsen cognitive functioning [25,26], and that the use of opioids to relieve pain induces cognitive dysfunctions, especially when some risks factors are present (e.g. female sex, advanced age, anxiety, depression, sleep disorders and tiredness) [27]. Additionally, we found that chronic pain patients were more affected by depression than those with acute pain, in agreement with previous findings [28,29]. Focusing on pain treatment, three key points should be discussed. The first one regards the prevalence of patients with no analgesic treatment: namely, 73.4% of chronic pain patients were not treated at 3
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Fig. 1. – Flow-chart. This flow-chart shows all the patients included in the REPOSI study from January 2012 to December 2014 and those included in the different steps of the analysis herein presented.
We acknowledge that the main limit of this analysis is that the REPOSI data collection system is not specifically addressed to evaluate pain features and therapy. In addition, available pain data regarded a reduced number of patients compared to the total sample enrolled in the whole register.
clinically relevant result implies a pain rating decrease of 2 points on the 0–10 scale by comparing pain perception after and before the treatment, or the reduction by at least 33% of pain intensity [30]. Moreover, reductions in pain intensity ≥30% and ≥ 50% refer to a clinically relevant and a substantial improvement of pain control, respectively [31]. In our analysis, the average reduction of pain was 20–25%, thus not reaching the forementioned criteria. These results lead us to suspect that the choice of treatment was not fully appropriate and thus only partially effective. This may depend on the daily doses, the pain drug association, other strategies as opioid switch in case of analgesic inefficacy, or on the interactions with other therapies. All in all, we believe that undertreatment and poor pain relief reflect an underestimation of the importance of pain in the elderly and/or the potential poor expertise on pain assessment and treatment by the physicians involved.
5. Conclusion In summary, we have shown that in spite of the fact that chronic pain is highly prevalent in the elderly population admitted to the internal medicine wards, analgesic treatment is not always considered and when a pharmacological approach is implemented, it appears to be quite ineffective. These results focus on the need for a greater attention to the problem and also highlight the need for an accurate knowledge about pain assessment and therapy. Pain and its treatment are not 4
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[3]
[4] [5] [6] [7]
[8] [9] [10]
[11]
Fig. 2. – Figure: Pharmacological treatment of chronic pain. Representation of the percentage of administrated analgesic drugs per each considered class at the time of admission, during hospital stay and at discharge. Abbreviations: WHO2 = World Health Organization – Step2; WHO3 = World Health Organization – Step3; NSAIDS = non-steroidal anti-inflammatory drugs; H-Stay = hospital stay; Neurop.Adjuvant = anti-neuropathic adjuvant. All data are expressed as percentages.
[12]
Table 2 – Chronic pain ratings at admission and discharge.
[16]
NRS admission
[13] [14] [15]
[17]
NRS discharge
[18] Patients treated at both admission and discharge (N = 26) Patients not treated at admission but treated at discharge (N = 27) Patients treated neither at admission nor at discharge (N = 52)
4,0 ± 2,4
4,3 ± 1,9
5,0 ± 2,3
4,1 ± 2,0
5,2 ± 2,1
5,1 ± 2,1
[19]
[20]
Average of pain ratings of patients with chronic pain by means of the 0–10 NRS at admission and discharge. Differences have been made for patients' classification by considering the pharmacological analgesic approach adopted for each patient. Abbreviations: NRS = numeric rating scale. All data are expressed are mean values ± SD.
[21] [22]
[23]
trivial issues and physicians must be aware of it, and be able to manage it properly in order to provide the best therapeutic outcome.
[24]
Conflict of interests
[26]
[25]
[27]
All authors have no conflict of interests to declare. Appendix A. Supplementary data
[28]
Supplementary data to this article can be found online at https:// doi.org/10.1016/j.ejim.2018.05.031.
[29]
[30]
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Contents lists available at ScienceDirect
European Journal of Internal Medicine journal homepage: www.elsevier.com/locate/ejim
Original Article
Prevalence, characteristics and treatment of chronic pain in elderly patients hospitalized in internal medicine wards ⁎
Nicole Corsia, , Anna Robertoa, Laura Cortesib, Alessandro Nobilib, Pier Mannuccio Mannuccic, Oscar Corlia, REPOSI Investigators1 a
Pain and Palliative Care Research Unit, Oncology Department, IRCCS-Mario Negri Institute for Pharmacological Research, Milan, Italy Quality Assessment of Geriatric Therapies and Services Laboratory, Neuroscience Department, IRCCS-Mario Negri Institute for Pharmacological Research, Milan, Italy c Scientific Direction, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy b
A R T I C LE I N FO
A B S T R A C T
Keywords: Aging Chronic pain Undertreatment Analgesic treatment Pain management
Background: Chronic pain is a frequent characteristic of elderly people and represents an actual and still poorly debated topic. Objective: We investigated pain prevalence and intensity, and its pharmacological therapy in elderly patients hospitalized in 101 internal medicine wards. Methods: Taking advantage of the “REgistro POliterapie Società Italiana Medicina Interna” (REPOSI), we collected 2535 patients of whom almost a quarter was older than 85 years old. Among them, 582 patients were affected by pain (either chronic or acute) and 296 were diagnosed with chronic pain. Results: Patients with pain showed worse cognitive status, higher depression and comorbidities, and a longer duration of hospital stay compared to those without pain (all p < .0366). Patients with chronic pain revealed lower level of independency in their daily life, worse cognitive status and higher level of depression compared to acute pain patients (all p < .0156). Moreover, most of them were not treated for pain at admission (73.4%) and half of them was not treated with any analgesic drug at discharge (50.5%). This difference affected also the reported levels of pain intensity. Patients who received analgesics at both admission and discharge remained stable (p = .172). Conversely, those not treated at admission who received an analgesic treatment during the hospital stay decreased their perceived pain (p < .0001). Conclusions: Our results show the need to focus more attention on the pharmacological treatment of chronic pain, especially in hospitalized elderly patients, in order to support them and facilitate their daily life after hospital discharge.
1. Introduction The elderly population is progressively increasing worldwide and chronic pain represents a characteristic among 66% of people aged over 65 years old [1]. Women are generally more likely affected by chronic pain than men [1–3]. Management of chronic pain in the elderly is still challenging, due to several age-related physiological changes causing pharmacokinetic and pharmakodynamic issues [4], and to the wide spectrum of primary diseases and comorbidities that usually include such chronic conditions as impaired sensory and cognitive capacities, abnormal kidney and cardiovascular functioning [5–7], diabetes mellitus, hypertension [8], depression, hip fracture, stroke, colorectal and lung cancer [9]. Among the risk factors affecting mortality, comorbidities are considered equally important as the main disease, being
⁎
1
present in approximately 89% of the discharged patients and in approximately 97% of those who died during the hospital stay [8]. Many of these comorbidities are themselves causes of pain. There is a wide agreement on the multidisciplinary approach necessary to assess and relieve pain in the elderly [10–14], since its inadequate recognition and treatment lead to a high probability of adverse negative outcomes such as functional impairment, falls, slower rehabilitation, mood alterations (e.g. depression and anxiety), reduction of socialization, deterioration of nutritional status, sleep disorders and overall a reduced quality of life [15,16]. Generally, from a pharmacological perspective, opioids are considered as the most powerful painkillers. An Italian study [17] based on the “REgistro POliterapie Società Italiana Medicina Interna” (REPOSI) showed that patients with chronic pain were prescribed with a rate of opioids prescription that increased from 3.8% to 5.8% when
Corresponding author at: Pain and Palliative Care Research Unit, Oncology Department, IRCCS Mario Negri Institute for Pharmacological Research, Via G. La Masa 19, Milan, Italy. E-mail address: [email protected] (N. Corsi). Please, refer to the Supplementary Data, Appendix.
https://doi.org/10.1016/j.ejim.2018.05.031 Received 16 February 2018; Received in revised form 10 May 2018; Accepted 23 May 2018 0953-6205/ © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
Please cite this article as: Nicole, C., European Journal of Internal Medicine (2018), https://doi.org/10.1016/j.ejim.2018.05.031
European Journal of Internal Medicine xxx (xxxx) xxx–xxx
N. Corsi et al.
comparing admission with discharge. Moreover, more than 50% of patients were administered with five or more different drugs, highlighting that the prescription of opioids is often associated with polypharmacy. These co-treatments may induce new clinical issues due to drug-to-drug interactions or drug-related adverse events. For instance, sedation and respiratory depression might occur when opioids are administered together with anticonvulsants, benzodiazepines, antipsychotics, selective serotonin reuptake inhibitors and antidepressants. These interactions highlight a potential relation between opioid-related mortality and medicines commonly used for chronic pain [18]. Considering the need to increase knowledge on pain in the hospitalized elderly, we chose to analyze the data from REPOSI with the goal to investigate pain prevalence and intensity, and its pharmacological management in elderly patients hospitalized in internal medicine and geriatric wards, with a special focus on the subset of those with chronic pain.
classifications are described elsewhere [19]. The pharmacological therapy was encoded according to the Anatomical Therapeutic Chemical (ATC) classification system and gathered into different categories of prescribed drugs: nonsteroidal anti-inflammatory drugs (NSAIDs, such as aspirin, ibuprofen, ketorolac, ketoprofen, COX2-inhibitors), paracetamol, opioids (WHO step 2, weak opioids such as codeine and tramadol; WHO step 3, strong opioids such as morphine, hydromorphone, methadone, fentanyl, oxycodone) adjuvant analgesics (such as tricyclic antidepressants, anticonvulsants, corticosteroids, bisphosphonates). The nature of pain (acute vs. chronic) was first assessed by the physician and then patients were asked to rate the level of perceived pain on a numeric rating scale (NRS), ranging from 0 (no pain) to 10 (the worst imaginable pain).
2. Materials and methods
Characteristics of patients with or without pain, and those with acute or chronic pain were compared using univariate analysis by means of chi-squared tests for categorical variables, and t-tests or analysis of variance (ANOVA) for continuous variables. The odds ratio (ORs) for patients administered with analgesic treatment compared to those not treated were analyzed using logistic regression models adjusting for age, sex, type of pain, functional and cognitive status, and depression. Analyses were performed using JMP Pro 13 (SAS Institute Inc. Cary. NC. USA) and Stata 13.0 (Stata Corp LP, College Station, Texas, USA). P-values < .05 were considered statistically significant.
2.2. Statistical analysis
From January 2012 to December 2014, 101 centers (86 from Italy and 15 from Spain) participated in the REPOSI register, a collaborative network between the Italian Society of Internal Medicine (SIMI, Societa` Italiana di Medicina Interna), the IRCCS Mario Negri Institute of Pharmacological Research and the IRCCS Ca′ Granda Maggiore Policlinico Hospital Foundation. The design of REPOSI was previously described [19]. This network aims to assess the prevalence of multiple diseases and pharmacological treatments of elderly people hospitalized in internal medicine wards in order to describe the relation between the clinical characteristics of the patients and the appropriateness of prescribed drugs. Additionally, it aims to evaluate the clinical status and drug prescription at admission, discharge and 3-month follow-up, the latter being verified by phone calls. The REPOSI network enrolled patients consecutively admitted to the participating hospital wards during a period of 4 weeks, 3 months apart from each other (in February, June, September, December 2012 and 2014). Inclusion criteria were age ≥ 65 years old and acceptance to sign the informed consent. Exclusion criteria included seriousness of patient's clinical condition and admission in terminal state. Participants signed the informed consent approved by the ethics committee of the IRCCS Ca′ Granda Maggiore Policlinico Hospital Foundation, Milan. 2535 patients were enrolled (2366 Italian and 169 Spanish). Among them, 5 were excluded because of missing information on the main outcome (pain), and 19 because they had post-operative pain, that is different in nature and treatment compared to chronic pain. Table 1 shows the social, educational, and clinical characteristics of the examined sample, distinguishing the general participants from those with pain, acute or chronic. Additionally, with the goal to evaluate the evolution of chronic pain from admission to discharge, we further excluded 63 patients because death occurred during hospitalization, transfer or missing data, and 124 patients who reported pain at admission but not at discharge. All the collected data were monitored by a central institution (Mario Negri Institute) for consistency, accuracy (with contacts of the peripheral clinical centers if necessary) and statistical analysis.
3. Results Results showed that among 2511 patients eligible for the analysis, 659 suffered from pain and 1852 did not (see the flow-chart, Fig.1). Among those with pain, 54.2% were women and pain patients differed from those without pain for living arrangements (p < .0001) and sex distribution (p = .0061). Patients suffering from pain showed worse cognitive status (p = .0366), higher levels of depression (p = .0004) and number of comorbidities (p = .0004), and a longer duration of hospital stay (p = .0026) compared to those who did not report pain (Table 1). Among 582 patients with pain, those with acute pain were comparable in number to those with chronic pain (286 and 296, respectively). There were lower level of independency in the activities of daily life (p < .0001), worse cognitive status (p = .0156) and higher level of depression (p = .0112) in the chronic pain compared with the acute pain population (Table 1). The multivariate analysis to check any possible influencing role of geriatric assessment variables in the administration of analgesic treatment showed that the worse the cognitive status, the lower the probability to be administered with WHO2 opioids (p = .005), and that the better the functional status, the higher the probability to be administered with WHO3 opioids (p = .020). However, no additional significances were found (Supplementary Data, Supplementary Table). By focusing on chronic pain patients who reported pain at both admission and discharge (N = 109), most of them were not treated for pain at the time of admission (73.4%). The remaining patients were already treated at admission with one analgesic drug (i.e. monotherapy, 22%) or with two or more drugs (i.e. polytherapy, 4.6%). At discharge, half of the chronic pain patients received no analgesic prescription (50.5%), the other half received a monotherapy (33.9%) or polytherapy (14.7%) analgesic prescription. By analyzing the type of analgesics, most chronic pain patients were treated with WHO-step 3 drug at admission (11.9%) but with WHO-step 2 during the hospital stay (19.2%) and at discharge (17.6%) (Fig.2). Our analysis on pain intensity showed a slight decrease in pain reports comparing admission (NRS pain average 4.9) with discharge (NRS pain average 4.7), although the difference was not statistically significant (p = .1532). Those patients who received an analgesic
2.1. Data collection All data obtained during the visits were entered into a standardized web-based case report form by the physician who attended the assessment. All the personnel involved in data collection was trained prior to the starting date in order to standardize the procedure of patient inclusion and evaluation. The following data were recorded for each patient: socio-demographic characteristics, body mass index, risk factors, severity and comorbidity index, cognitive functioning assessment, duration of hospital stay, state of patients at discharge and pharmacological therapy. Moreover, we recorded both the intensity and nature (acute vs. chronic) of pain. The evaluating tools and diagnosis 2
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Table 1 - Sample descriptive characteristics.
Age (mean ± SD) Age classes (N, %) 65–74 75–84 ≥ 85 Education (years) (mean ± SD) Marital status (N, %) Single Married Widow/er Living arrangement (N, %) Alone With spouse With sons With spouse and sons Other BMI (mean ± SD) SI at admission (mean ± SD) CI at admission (mean ± SD) BI at admission (mean ± SD) SBT (mean ± SD) GDS (mean ± SD) Duration of hospital stay. (mean ± SD) State of the patients at discharge (N, %) Discharge Discharge Critical condition Transferred Dead Total number of drugs (mean ± SD) GFR [20] (mean ± SD)
General population
Pain population
N = 1852
N = 659
79.3 ± 7.6
78.9 ± 7.1
541 800 509 6.2 ± 4.6
29.2 43.2 27.5
157 1006 613 346 836 255 106 145 25.9 ± 5.0 1.6 ± 0.3 3.0 ± 1.9 78.0 ± 30.1
Chronic pain population
Acute pain population
N = 296
N = 286
0.3115
79.1 ± 7.2
78.7 ± 7.2
0.3380
91 131 74 5.9 ± 4.5
30.7 44.3 25
198 299 162 6.2 ± 4.6
30.0 45.4 24.6
8.5 54.7 33.3
69 320 241
10.5 48.8 36.7
0.1721
31 140 114
19.6 47.4 14.5 6 8.2
184 266 96 37 41 25.9 ± 5.2 1.7 ± 0.4 3.4 ± 2.0 80.0 ± 26.4
28.8 41.7 15.0 5.8 6.4
< 0.0001
0.9085 < 0.0001 < 0.0001 0.1073
75 120 47 18 21 26.2 ± 5.8 1.8 ± 0.3 3.5 ± 2.0 75.4 ± 28.6
0.0366 0.0004 0.0026
9.1 ± 2 1.6 ± 1.3 13.4 ± 12.2
0.1425
248 3 30 15 6.5 ± 3.45 61.1 ± 25.4
9.0 ± 8.1 1.2 ± 1.3 11.6 ± 9.4 1623 16 131 79 5.5 ± 3.1 59.4 ± 24.2
p
0.7018
8.3 ± 7.1 1.4 ± 1.3 12.9 ± 10.5 87.8 0.9 7.1 4.3
558 6 65 30 5.9 ± 3.4 60.1 ± 24.0
84.7 0.9 9.9 4.5
0.0115 0.5189
p
0.5833
81 134 71 6.2 ± 4.5
28.3 46.8 24.8
10.5 47.5 38.6
31 142 97
10.9 50.0 34.1
0.4830
26 41.7 16.3 6.2 7.3
84 120 38 15 15 25.6 ± 4.4 1.7 ± 0.4 3.3 ± 2.0 84.5 ± 23.7
30.1 43.1 13.6 5.4 5.4
0.7624
0.5677
0.1954 0.0214 0.0966 < 0.0001
7.6 ± 6.9 1.3 ± 1.2 12.5 ± 8.8 83.8 1 10.1 5.1
250 3 25 8 5.5 ± 3.2 59.5 ± 22.0
0.7766
0.0156 0.0112 0.3241 83.8 1.0 8.7 2.8
0.4896
0.0002 0.4056
Abbreviations: BMI = body mass index; SI = severity index; CI = comorbidity index; BI = Barthel index; SBT = short blessed test; GDS = geriatric depression scale; GFR = glomerular filtration rate.
the time of admission. Thus, undertreatment is related to the choice of previous physicians (e.g. family practitioners) rather than internal medicine physicians. However the data recorded at hospital discharge showed that 50.5% of patients that reported chronic pain still remained untreated, thus extending the concern for undertreatment also to the hospital stay and physicians. A second observation regards the choice of the administered analgesics. At admission, patients with chronic pain were treated with one (i.e. monotherapy, 22%) or more (i.e polytherapy, 4.6%) analgesic drugs. During the hospital stay, physician did apparently modify the pharmacological approach in order to better manage patients' pain, so that at discharge 48.6% of patients were treated with monotherapy (33.9%) or polytherapy (14.7%). Regarding the type of analgesic, all the medications of the classes (NSAIDs, paracetamol, opioids and adjuvants) were administered to a greater extent at the time of discharge than at admission. The increasing administration of NSAIDs, almost doubled at the time of discharge, is of concern because their use needs caution due to the high risk of adverse effects in the elderly [14]. At the same time, paracetamol, despite being considered as a safe drug in the elderly, was less prescribed at the time of discharge. A third observation regards the questionable efficacy of the administered pain medications. Results showed that the average pain intensity reported by the chronic pain patient population decreased from 4.9 to 4.7 out of 10 comparing admission to discharge. By separately analyzing pain intensity of treated vs. untreated patients at both admission and discharge, it turned out that the former rated their pain intensity 4 of 10 points, while the latter scored about 5 of 10 points at both admission and discharge. The difference between pain ratings of treated and untreated patients is clinically quite unsatisfactory. According to the Farrar criteria, a good response to analgesics should be reflected in a difference in pain intensity before and after treatment. A
treatment at both admission and discharge (N = 26) remained stable (4.0 ± 2.4 vs. 4.3 ± 2.0, respectively; p = .172). Conversely, those not treated at admission but who received analgesics during the hospital stay (N = 27) decreased significantly the perceived level of pain (5.0 ± 2.3 vs. 4.1 ± 2.0; p < .0001) (Table 2). 4. Discussion Our goal was to analyze prevalence, nature and severity of pain, and its pharmacological treatment in elderly patients hospitalized in internal medicine wards. In our sample, 582 of 2511 patients (23.2%) experienced pain. Among them, 296 (i.e., 11.8% of the whole sample) had chronic pain. This rate, much lower than usually reported, is more likely to represent an underestimation in the diagnosis of pain rather than an effectively less painful population. The presence of pain was associated with worse severity and comorbidity index, cognitive and depressive status, and number of administered drugs at admission. Furthermore, the presence of pain led to a longer hospital stay. By comparing chronic with acute pain patients, we found that autonomy level, depressive status and cognitive functions were worse in chronic pain patients. This decline of cognitive functions is in accordance with previous findings [21–24], considering that pain itself contributes to worsen cognitive functioning [25,26], and that the use of opioids to relieve pain induces cognitive dysfunctions, especially when some risks factors are present (e.g. female sex, advanced age, anxiety, depression, sleep disorders and tiredness) [27]. Additionally, we found that chronic pain patients were more affected by depression than those with acute pain, in agreement with previous findings [28,29]. Focusing on pain treatment, three key points should be discussed. The first one regards the prevalence of patients with no analgesic treatment: namely, 73.4% of chronic pain patients were not treated at 3
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Fig. 1. – Flow-chart. This flow-chart shows all the patients included in the REPOSI study from January 2012 to December 2014 and those included in the different steps of the analysis herein presented.
We acknowledge that the main limit of this analysis is that the REPOSI data collection system is not specifically addressed to evaluate pain features and therapy. In addition, available pain data regarded a reduced number of patients compared to the total sample enrolled in the whole register.
clinically relevant result implies a pain rating decrease of 2 points on the 0–10 scale by comparing pain perception after and before the treatment, or the reduction by at least 33% of pain intensity [30]. Moreover, reductions in pain intensity ≥30% and ≥ 50% refer to a clinically relevant and a substantial improvement of pain control, respectively [31]. In our analysis, the average reduction of pain was 20–25%, thus not reaching the forementioned criteria. These results lead us to suspect that the choice of treatment was not fully appropriate and thus only partially effective. This may depend on the daily doses, the pain drug association, other strategies as opioid switch in case of analgesic inefficacy, or on the interactions with other therapies. All in all, we believe that undertreatment and poor pain relief reflect an underestimation of the importance of pain in the elderly and/or the potential poor expertise on pain assessment and treatment by the physicians involved.
5. Conclusion In summary, we have shown that in spite of the fact that chronic pain is highly prevalent in the elderly population admitted to the internal medicine wards, analgesic treatment is not always considered and when a pharmacological approach is implemented, it appears to be quite ineffective. These results focus on the need for a greater attention to the problem and also highlight the need for an accurate knowledge about pain assessment and therapy. Pain and its treatment are not 4
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[3]
[4] [5] [6] [7]
[8] [9] [10]
[11]
Fig. 2. – Figure: Pharmacological treatment of chronic pain. Representation of the percentage of administrated analgesic drugs per each considered class at the time of admission, during hospital stay and at discharge. Abbreviations: WHO2 = World Health Organization – Step2; WHO3 = World Health Organization – Step3; NSAIDS = non-steroidal anti-inflammatory drugs; H-Stay = hospital stay; Neurop.Adjuvant = anti-neuropathic adjuvant. All data are expressed as percentages.
[12]
Table 2 – Chronic pain ratings at admission and discharge.
[16]
NRS admission
[13] [14] [15]
[17]
NRS discharge
[18] Patients treated at both admission and discharge (N = 26) Patients not treated at admission but treated at discharge (N = 27) Patients treated neither at admission nor at discharge (N = 52)
4,0 ± 2,4
4,3 ± 1,9
5,0 ± 2,3
4,1 ± 2,0
5,2 ± 2,1
5,1 ± 2,1
[19]
[20]
Average of pain ratings of patients with chronic pain by means of the 0–10 NRS at admission and discharge. Differences have been made for patients' classification by considering the pharmacological analgesic approach adopted for each patient. Abbreviations: NRS = numeric rating scale. All data are expressed are mean values ± SD.
[21] [22]
[23]
trivial issues and physicians must be aware of it, and be able to manage it properly in order to provide the best therapeutic outcome.
[24]
Conflict of interests
[26]
[25]
[27]
All authors have no conflict of interests to declare. Appendix A. Supplementary data
[28]
Supplementary data to this article can be found online at https:// doi.org/10.1016/j.ejim.2018.05.031.
[29]
[30]
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