Dig Dis Sci DOI 10.1007/s10620-014-3462-2

REVIEW

Medical and Surgical Complications of Inflammatory Bowel Disease in the Elderly: A Systematic Review Dennis L. Shung • Bincy Abraham Joseph Sellin • Jason K. Hou



Received: 7 October 2014 / Accepted: 21 November 2014 Ó Springer Science+Business Media New York (Outside the USA) 2014

Abstract Background/Aims The complications of therapy, hospitalization, and surgery related to inflammatory bowel disease (IBD) in the elderly are not well described. While multiple reviews have described the management and complications of elderly patients with IBD, none have been performed in a systematic fashion. Methods We performed a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to evaluate the association between elderly patients with IBD and complications from therapy, hospitalizations, and surgery. Eligible studies were identified via structured keyword searches in PubMed and manual literature searches. Results A total of 5,644 publications were identified. Of these, fourteen studies met inclusion criteria, encompassing 963 elderly IBD patients (113 Crohn’s disease and 850 ulcerative colitis patients), over 37,000 hospitalizations of elderly IBD patients and over 4,500 controls. Consistent

associations were observed between increased age and higher nocturnal stool frequency post-ileal pouch anal anastomosis. Only two studies met inclusion criteria for medication-related complications, one observed an increased mortality and infection risk among elderly patients treated with tumor necrosis factor antagonists and the other observed increased hospital-related complications among elderly patients treated with steroids. Conclusions Elderly patients with IBD are at an increased risk of hospital- and therapy-related complications. We found a paucity of high-quality studies evaluating outcomes in elderly patients with IBD. Further studies of elderly patients with IBD are needed to further evaluate the effect of age on medical and surgical complications. Keywords Crohn’s disease  Ulcerative colitis  Elderly  Complications  Postoperative complications

Introduction

D. L. Shung  J. Sellin  J. K. Hou (&) Baylor College of Medicine, One Baylor Plaza BCM:901, Houston, TX 77030, USA e-mail: [email protected] B. Abraham The Houston Methodist Hospital, Houston, TX, USA J. K. Hou Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA J. K. Hou VA HSR&D Center for Innovations in Quality, Effectiveness and Safety, Houston, TX, USA

As the population ages, the proportion of elderly patients with inflammatory bowel disease (IBD) is expected to increase. Current epidemiological estimates suggest that 10–15 % of IBD patients are age [60 years at diagnosis, with equal distribution between Crohn’s disease (CD) and ulcerative colitis (UC) [1, 2]. A recent systematic review reported the annual incidence of IBD in North America to be 19.2 per 100,000 person-years for UC (worldwide 6.3–24.3 per 100,000 person-years) and 20.2 per 100,000 personyears for CD (worldwide 5–20.2 per 100,000 person-years) [3]. As IBD is a chronic disease without significant associated mortality, the proportion of elderly IBD patients is expected to increase over time [4]. However, the designation of ‘‘elderly’’ is not well defined in the literature; the term has

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been assigned to a range of groups greater than 40–75 years of age [5]. The classical bimodal distribution of IBD is between 20 and 30 years and 50–80 years, and C50 had been considered as a cutoff for ‘‘elderly’’ [2]. More recent reviews have used a definition of age C60 or C65 as elderly [4, 6–11]. Complications related to medical and surgical treatment among elderly patients with IBD are poorly described. Elderly age has been suggested as an independent risk factor for postoperative complications in CD patients [12]. Management of postsurgical, hospitalization-related, and therapeutic outcomes in IBD is complicated by polypharmacy and medical comorbidities such as renal insufficiency and cardiovascular disease [13–16]. In addition, elderly patients are often excluded from randomized clinical trials [17]. To date, many studies involving treatment of and complications among elderly patients with IBD have been small in size with limited generalizability [6, 18–20]. There has been no systematic review of the association between elderly age and intervention-related complications in elderly IBD patients. We therefore performed a systematic review of studies of postsurgical, hospitalization-related, and therapeutic complications in elderly IBD patients.

following criteria: relevance to therapy, complications or hospitalizations, study design, and sample size of at least 50 IBD patients C50 years old. Citations were independently reviewed by two investigators (DS and JH) to determine eligibility. Discrepancies were resolved by consensus of the study team. Data Extraction With the use of standardized forms, the following data points were collected for each study: location, design, data source, number of patients with UC or CD, definition of elderly age and of reference group if applicable, and sex distribution. When studies contained insufficient information to assess their eligibility or extract relevant data, the corresponding authors were contacted for further information. Studies that did not provide the number of unique patients were eligible for inclusion if the number of hospitalizations of elderly IBD patients was greater than 200. Post-IPAA complications data were collected and categorized into bowel movements, bowel incontinence, and pouch failure. Complications from hospitalizations were further categorized into infection or mortality. Given the heterogeneity among studies, quantitative summaries and pooling of the data were not performed.

Methods Search Strategy

Results

We performed a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [21]. We conducted a structured search of PubMed from January 1, 1992 to April 22, 2013, using the medical subject heading (MeSH) terms ‘‘aged,’’ ‘‘geriatrics,’’ ‘‘age factors,’’ and all fields search of ‘‘geriatrics’’ or ‘‘elderly’’ using the explode function for subgroup terms with operators (‘‘and,’’ ‘‘or’’) for MeSH terms ‘‘inflammatory bowel diseases,’’ ‘‘colitis, ulcerative,’’ and ‘‘Crohn’s Disease.’’ Filters were used to exclude publication types of ‘‘Case Reports,’’ or ‘‘in vitro,’’ and MeSH terms ‘‘Child,’’ ‘‘Infant,’’ ‘‘Cells,’’ or ‘‘Genetic Phenomena.’’ There were no language restrictions. Eligible studies and relevant review articles were hand-searched to identify additional studies missed by database searches.

Search Results

Eligibility Criteria Fully published case–control and cohort studies describing complications related to medical or surgical treatment among elderly patients with IBD were eligible for inclusion. We included studies that defined elderly patients as at least 50 years of age. Titles and abstracts were screened to identify relevant articles, which were assessed for the

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A total of 5,644 publications were identified (Fig. 1). Of these, 67 studies reviewed in English and Japanese, fourteen met inclusion criteria (Table 1). The included studies encompassed 963 elderly IBD patients (113 CD and 850 UC patients), over 37,000 hospitalizations of elderly IBD patients, and over 4,500 controls. Twelve studies were retrospective, and two studies were prospective. Medication-Related Complications A total of two studies evaluating medication-related severe infections and mortality among elderly patients with IBD were eligible for inclusion (Table 2). A retrospective case– control study of patients [22] with IBD reported the association of tumor necrosis factor antagonist (anti-TNFs) use in non-hospitalized elderly patients and complications of mortality and infections. Elderly patients with IBD who received anti-TNFs had significantly increased infections compared to the elderly ([65 year old) patients not receiving anti-TNFs (11.5 vs. 0.5 %, p \ 0.001) and compared to adult (\65 years old) IBD patients receiving anti-TNFs (11.5 vs. 2.6 %, p \ 0.01) and higher rates of

Dig Dis Sci

Fig. 1 Flowchart diagram detailing search strategy of PubMed from all available articles from January 1, 1992 through February 2, 2013. 5,644 abstracts were identified using the described search criteria and

reviewed. Additional eligible studies and relevant review articles were hand-searched to identify additional studies missed by the PubMed query

death (elderly with anti-TNF 10.5 %; elderly without antiTNF 2.1 %; \65 year old with anti-TNF 1.1 %, p \ 0.01) [22]. Examining a hospital discharge database of elderly patients with Crohn’s disease, Akerkar et al. found no increased risk of severe infection or mortality associated with steroid therapy in hospitalized elderly IBD patients. However, those treated with high-dose IV or oral steroids had significantly increased risk for hypertension [RR 1.46 (95 % CI 1.09–1.95)] and hypokalemia [RR 1.59 (95 % CI 1.06–2.37)] compared to those not treated with steroids [23].

Hospitalization-Related Complications Mortality Two studies reporting hospitalization-associated mortality met inclusion criteria (Table 2). Both studies found increased mortality among hospitalized elderly IBD patients compared to younger patients [24, 25]. A multicenter retrospective study [24] reported an increased mortality risk in hospitalized aged (51–65 years old) UC patients with Clostridium difficile compared to hospitalized UC patients \50 years old with

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Dig Dis Sci Table 1 Characteristics of included studies of complications in elderly IBD patients Study

Location

Design

UC total (#)

CD total (#)

Age definition elderly (yrs)

UC elderly (# [ 50)

CD elderly (# [ 50)

Age definition Ref. group (yrs)

Akerkar [23]

United States

SC retrospective CC

0

115

C50

0

55

C50

0

Almogy [31]

United States

SC retrospective cohort

113

0

C65

113

Ananthakrishnan [24]

United States

MC retrospective cohort

205a

89a

C50

216a

\50

Ananthakrishnan [26]

United States

MC retrospective CC

645a

1,008a

C50

1,455a

\50

C65

35,573a

4

C50

51

0

\50

a

C65

\65

Ananthakrishnan [25]

United States

MC retrospective cohort

140,996

Bauer [34]

United States

SC retrospective cohort

374

Chapman [32]

United States

SC prospective cohort

1,790

0

C45

62

0

\45

Cottone [22]

Italy

MC retrospective CC

185

290

C65

37

58

\65

Delaney [18]

United States

SC prospective cohort

1,364

94

C45

135

0

\45

Ha [30]

United States

SC retrospective cohort

295

0

C50

140

0

\50

Ho [33]

United States

SC retrospective cohort

330

0

C50

103

0

\50

Longo [28]

United States

MC retrospective CS

259



C50

158

0

\50

Navaneethan [27]

United States

MC retrospective CS

18,883a

15,792a

C50

116a

76a

\50

Triantafillidis [29]

Greece

MC retrospective cohort

413

0

C60

51

0

\60

– N/A SC single center, MC multicenter, CC case–control, CS cross-sectional, UC ulcerative colitis, CD Crohn’s disease a

Hospitalizations;

b

diagnosis \64 y/o

Clostridium difficile [HR 2.03 (95 % CI 1.02–4.49)] [24]. A non-statistically significant trend of increased mortality was also observed among patients C65 compared to patients 19–50 [HR 2.14, (95 % CI 0.92–4.54)]. A retrospective cohort study of the Nationwide Inpatient Sample (NIS) [25] found increased mortality among hospitalized IBD elderly patients (C65 years old) compared to those \64 years old [adjusted OR 3.91 (95 % CI 2.50–6.11)]. Increased in-hospital mortality was observed for elderly IBD patients with fistulizing disease [adjusted OR 1.90 (95 % CI 1.32–2.73)], malnutrition [adjusted OR 1.86 (95 % CI 1.38–2.51)], hypovolemia [adjusted OR 2.01 (95 % CI 1.59–2.54)], and who required surgery [adjusted OR 2.71 (95 % CI 1.95–3.76)]. Bowel obstruction [adjusted OR 0.68 (95 % CI 0.50–0.93)] and anemia [adjusted OR 0.75 (95 % CI 0.59–0.97)] were associated with lower in-hospital mortality. No difference in mortality was seen based on IBD type. There was a significant increase in mortality in elderly versus younger IBD patients regardless of whether they underwent surgery [adjusted OR 2.46 (95 % CI 1.17–5.18)] or not [adjusted OR 4.84 (95 % CI 2.76–8.51)] [25]. No difference in length of stay, higher hospitalization costs, or increased postoperative stay in both hospitalized elderly CD and UC patients compared to young patients with IBD (18–64 years of age). Fracture One study reporting on fracture-related hospitalizations among elderly patients with IBD met inclusion criteria.

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Age was a significant predictor of fracture-related hospitalizations among elderly patients (C65 years old) with IBD (73.1 vs. 25.4 %, p \ 0.001), but not for aged patients (51–65 years old). In IBD patients hospitalized for fractures, the percentage of elderly patients (C65 year old) with hip fracture was significantly greater than the percentage of elderly patients (C65 year old) with non-hip (vertebral, wrist) fractures (80.2 vs. 58.6, 58.9 % p \ 0.001) [26]. Complications from Surgery and Endoscopy Endoscopy-Related Complications Only one study met inclusion criteria for endoscopy-related complications among elderly patients with IBD. A retrospective cross-sectional study of the NIS observed that older age was an independent risk factor for colonic perforation with colonoscopy in hospitalized IBD patients [adjusted OR 1.01, (95 % CI 1.006–1.015)] [27]. There were no differences in perforation risk based on IBD type. Surgery Rates Three studies reported low rates of total colectomy (0–2.1 %) and segmental colectomy (0–4 %) among elderly IBD patients [28–30]. A multicenter retrospective cohort study in Greece [29] observed that elderly UC patients (C60 years old) were less likely to undergo

Dig Dis Sci Table 2 Severe infections and mortality in hospitalized elderly IBD patients Study

Outcome

Group

Infection

p value

Death

p value

Cottone [22]

Severe infection

Anti-TNF \65 y/o

5/190 (3 %)

\0.01

2/190 (1 %)

\0.01

No anti-TNF C65 y/o

1/190 (1 %)

4/190 (2 %)

Biologic elderly

11/95 (12 %)

10/95 (11 %)

Akerkar [23] Ananthakrishnan [24]

Ananthakrishnan [25]

Any hospitalized infection Mortality with hospital-related C. difficile infection In-hospital mortality

No steroids

6/60 (ref)







Steroids

6/55 (RR 1.09)

0.37–3.18*





19–50 y/o

Ref





51–65 y/o





HR 2.03

1.02–4.49*

C65 y/o





HR 2.14

0.92–4.54*

18–64 y/o





Ref

C65 y/o





OR 3.91

2.50–6.11*

RR risk ratio, HR hazard ratio, OR odds ratio, ref reference, y/o years old, IBD inflammatory bowel disease * 95 % confidence interval

surgery compared to younger UC patients (5.9 vs. 18.2 %, p = 0.03) [29]. A single-center retrospective study [30] compared early-onset UC patients to late-onset UC patients and found that late-onset UC (diagnosed C50 years old) with or without systemic steroid therapy had no significant difference in requiring colectomy at 1 year of diagnosis compared to early-onset UC (18–30 years old) [30]. A retrospective cohort study of the Nationwide Inpatient Sample (NIS) [25] found no difference in rates of surgery for hospitalized elderly IBD patients (C65 years of age) compared to younger patients (18–64 years). Elderly UC patients were less likely to undergo surgery compared to younger UC patients [OR 0.70 (95 % CI 0.55–0.88)], but CD elderly patients show no difference in rate of surgery compared to younger CD patients [31]. Surgery-Associated Complications Three studies reporting surgery-associated complications among elderly IBD patients met inclusion criteria. A single-center retrospective study [31] reported major complications and death after surgery for UC. They reported surgical outcomes from 1960 to 1999 as three time periods: 1960–1984, 1985–1993, and 1994–1999. They observed a significant decrease over time in the composite end point of major complications and deaths among elderly UC patients, from 50 % in 1960–1984 to 27 % in 1994–1999, p \ 0.05. They also observed postoperative complication rates among patients C75 years old significantly decreased over a 40-year period (from 86 to 30 %, p \ 0.05 and age C75 years at surgery was not a predictor of adverse outcome [31]. A retrospective VA national database study of elderly UC patients [28] showed no statistically significant difference in surgical morbidity or 30-day mortality between total proctocolectomy (TPC) with ileostomy and

TPC with ileoanal anastomosis [28]. No difference in postoperative complication rate between elective and emergent surgery among elderly patients with UC was observed [28]. A retrospective cohort study of the Nationwide Inpatient Sample (NIS) [25] reported elderly IBD (C65 years of age) patients were more likely to suffer postoperative cardiovascular [OR 2.26 (95 % CI 1.13–4.54)] and pulmonary complications [OR 1.66 (95 % CI 1.12–2.48)] compared to younger patients (18–64 years) [25]. Post-Ileal Pouch Anal Anastomosis (IPAA) Function A total of four studies were included evaluating post-IPAA function among elderly patients with UC. Three studies reporting pouch failure after IPAA were eligible for inclusion (Table 3) [18, 32, 33]. The three studies showed conflicting results. One prospective study [18] of 1,895 patients with IPAA, including 42 patients C65 years of age, reported a significant difference in pouch failure rate by age. However, pairwise differences between age groups were not significant [18, 32, 33]. A second prospective study [32] included 2002 patients after IPAA (1,790 with UC, 65 patients C55 years of age) showed numerically lower pouch failure rates among patients C55 years of age compared to younger patients, but the difference was not statistically significant [32]. One retrospective study [33] observed higher pouch failure rates among patients 50–69 and C70 compared to younger patients, but the differences were not statistically significant [33]. Four studies examining the differences in bowel incontinence after IPAA between elderly and young patients were included (Table 4) [18, 32–34]. Two single-center studies [18, 32] found significantly increased nighttime bowel incontinence rates among in elderly patients

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Dig Dis Sci Table 3 Post-IPAA failure Study

Pouch failure rate (%) Ref

Case

p value

Chapman [32] Overall

5.9



\45/o

5.7



46–55 y/o

4.8



C55 y/o



1.6

\45 y/o 46–55 y/o

4.2 2.4

– –

56–65 y/o



5.9

C65 y/o



4.8

0.42

Delaney [18] \0.01*

Ho [33] \30 y/o

1.3



30–49 y/o

1.4



50–69 y/o



3.5

C70 y/o



11.8

0.20

IPAA ileal pouch anal anastomosis * No difference in pairwise comparisons Table 4 Post-IPAA bowel incontinence Study

Follow-up (years)

Bowel incontinence (%) Ref

Case

p value

Chapman [32] \45 y/o

C55 y/o

1

4.1 %

15.2 %

\0.01

3 5

3.4 % 4.5 %

13.5 % 6.7 %

\0.01 0.46

10

4.8 %

12.0 %

0.13

Daytime

\45 y/o

C55 y/o

1

9.4 %

26.1 %

\0.01

3

9.3 %

19.6 %

0.03

5

8.9 %

15.6 %

0.18

10

12.2 %

24.0 %

0.11

\45 y/o

56–65 y/o

1

34 %

50 %

\0.01

3

31 %

46 %

\0.01

5

35 %

48 %

0.22

10

39 %

39 %

0.72

\30 y/o 30–49 y/o

3.8 % 2.7 %

– –

0.30

50–69 y/o



0

C70 y/o



11.7 %

16 %

12 %

Nighttime

Delaney [18] Nighttime

Ho [33] Daytime

Bauer [34] Daytime

0.47

y/o years old, IPAA ileal pouch anal anastomosis, ref reference group

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(C55 years old) compared to younger patients at 3 years after IPAA (range 19.6–46 % for elderly vs. 9.3–31 % in non-elderly, p \ 0.05), but no difference after 3 years (range 15.6–48 % for elderly vs. 8.9–35 % for non-elderly, p [ 0.10 [18, 32]. One of these studies [18] found significantly increased daytime bowel incontinence rates in the first 3 years post-IPAA (13.5 vs. 3.4 %, p \ 0.01) [32]. Two other single-center retrospective cohort studies [33, 34] found no differences in daytime bowel incontinence between elderly (C50 years old) and younger IBD patients [33, 34]. Three studies reported on nocturnal bowel movement frequency among elderly UC patients after IPAA (Table 5) [18, 32, 33]. All three studies reported small, but statistically significant increases in nocturnal bowel movement frequency among elderly patients compared to young patients (range 1.9–2.0 vs. 1.4–1.7, p \ 0.05) [18, 32, 34]. However, long-term data regarding nocturnal bowel movement frequency were conflicting; two studies [32, 34] reported higher nocturnal bowel movement frequency among elderly patients 10 years after IPAA compared to younger patients (2.0 ± 0.8 vs. 1.7 ± 1.4, p \ 0.01 and 1.9 ± 0.3 vs. 1.4 ± 0.1, p = 0.02, respectively), and one study [18] showed lower nocturnal bowel movements among elderly patients at 10 years post-IPAA compared to younger patients (0.6 vs. 1.7, p = 0.02) [18, 32, 34]. Four studies reported daytime bowel movement frequency among elderly UC patients after IPAA [18, 32–34]. One study [18] showed a small, but statistically significant increase in daytime bowel movements at 5 years postIPAA based on age [5.9 (C65 years) vs. 5.7 (\45 years), p \ 0.05] [18]. Three other studies did not show any significant difference in daytime bowel movement frequency among elderly patients compared to younger patients [18, 32–34].

Discussion We performed a systematic review of medical and surgical complications among elderly patients with IBD. Fourteen studies were included, encompassing 963 elderly IBD patients, over 37,000 hospitalizations of IBD patients, and over 4,500 controls. We observed considerable variation among published studies in the definition of ‘‘elderly,’’ making any quantitative pooling of data impossible. In addition, most studies did not differentiate between early versus late-onset IBD. Recent studies have suggested that early- and late-onset IBD may have different characteristics; late-onset CD may have less extensive small bowel involvement and a lower risk of requiring surgery for nonneoplastic bowel disease [35, 36]. However, late-onset CD has also been associated with a delay in diagnosis

Dig Dis Sci Table 5 Post-IPAA daytime and nocturnal bowel movements Study

Follow-up (years)

Bowel movements (#) Ref

p value

Case

Chapman [32] Daytime 1

\45 y/o

C55 y/o

5.7 ± 2.3

6.0 ± 2.5

3

5.7 ± 2.2

5.4 ± 2.2

5

5.7 ± 2.4

5.9 ± 2.4

10

5.7 ± 2.7

5.3 ± 2.1

1

\45 y/o 1.5 ± 1.3

C55 y/o 2.0 ± 1.1

Nighttime

[0.05

\0.01

3

N/A

2.0 ± 1.4

5

N/A

1.9 ± 1.1

10

1.7 ± 1.4

2.0 ± 0.8

\45 y/o

C65 y/o

1

6.1

6

0.13

3

5.8

5.4

0.54

5

5.7

5.9

0.04

10

5.5

4.6

0.52

\45 y/o

C65 y/o

1.4

1.9

\0.01 \0.01

Delaney [18] Daytime

Nighttime 1 3

1.5

2

5

1.4

1.7

0.02

10

1.7

0.6

0.02

\30 y/o

5



0.40

30-49 y/o

6.4



50-69 y/o



8.5

C70 y/o



5.7

Daytime

\49 y/o

C50 y/o

5.0 ± 0.2

5.5 ± 0.3

Nighttime

\49 y/o

C50 y/o

1.4 ± 0.1

1.9 ± 0.3

Ho [33] Daytime

Bauer [34] 0.14 0.02

y/o years old, IPAA ileal pouch anal anastomosis, ref reference group

compared to early-onset CD [19, 37]. Late-onset UC has been associated with increased risk of toxic megacolon and mortality but similar risk of CRC as early-onset UC [38]. Apart from the study by Ha et al. that compared early- and late-onset UC, we were unable to differentiate or make comparisons between early- and late-onset IBD based on the included studies. We observed a paucity of studies reporting medical and surgical complications particularly among elderly patients with CD. The studies that met our inclusion criteria were predominantly among patients with UC; the significance of a predominance of UC studies in elderly patients over CD studies is unclear. This difference may be explained in part

by the clearly defined surgical therapeutic options for UC versus CD and the availability of post-IPAA studies among patients with UC. Prior studies have reported elderly patients were more likely to receive a TPC/ileostomy versus TPC with IPAA due to concern for adverse postsurgical and functional outcomes in elderly IBD patients [21, 28]. However, the studies in this systematic review suggest that functional outcomes after IPAA in the elderly are generally well tolerated, with no significant difference in daytime functional impairment compared to younger patients. We observed increased nocturnal bowel incontinence for the first 3 years post-IPAA in elderly UC patients undergoing IPAA as well as a small, but statistically significant, association between increased nocturnal bowel movements and age in UC patients undergoing IPAA. Although the differences in functional outcomes between elderly and young patients who had undergone IPAA were statistically significant, the differences of less than one bowel movement per night may not be clinically significant. There was no consistent association between age and post-IPAA failure rates. Additionally, no difference was found in surgical morbidity or 30-day mortality between the TPC with IPAA and TPC with ileostomy regardless of age. We observed a large gap in the literature regarding the safety of IBD medications among elderly patients with IBD. There are data to suggest in other disease that elderly patients may be more at risk from medication-related complications. Polypharmacy has been associated with adverse drug reactions (ADRs), and elderly patients are more likely to receive more medications [39]. Elderly patients admitted to hospitals and in nursing homes and have been found to have polypharmacy associated with ADRs [40–43]. Opioids in particular have been associated with increased ADRs in elderly [44]. However, only two studies met inclusion criteria in our review regarding medication-related complications among elderly patients with IBD. Elderly patients with IBD are more likely to have substantial comorbidities such as diabetes, renal failure, congestive heart failure, and neuropathy compared to younger patients with IBD, raising concern of interactions and contraindications with the use of medications for IBD. In fact, Feagins et al. [20] observed younger patients with CD (\40 years old) had significantly higher rates of use of anti-TNFs compared to older patients. A multicenter retrospective case–control study included in this review observed increased infection and mortality among elderly IBD patients receiving anti-TNFs compared to elderly IBD patients not on anti-TNFs as well as young IBD patients on anti-TNFs. However, this study was retrospective and therefore unable to account for selection bias based on disease severity and medication indication. Although they did not meet inclusion criteria based on the lack of

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definition of an elderly population, several safety registries also support the concern of an increased risk of infection and death based on age. Data from the TREAT registry of infliximab for Crohn’s disease have observed an increased mortality [adjusted HR 1.078 (95 % CI 1.067–1.090)], serious infection [adjusted HR 1.013 (95 % CI 1.004–1.023)], and malignancy [adjusted HR 1.59 (95 % CI 1.42–1.75] with increasing age [45, 46]. Infliximab exposure was associated with a higher risk of serious infection [adjusted HR 1.431 (95 % CI 1.110–1.844)], but not mortality among; however, infection and mortality rates among elderly patients based on infliximab exposure were not specifically reported [46]. The only study eligible for inclusion on steroids among elderly patients with IBD did not demonstrate an increased risk of infection or mortality among steroid-exposed patients; however, steroids were associated with significantly prolonged hospital stay, risk for hypertension, hypokalemia, and altered mental status among elderly patients with IBD compared to those not treated with steroids [23]. There were no studies that met our inclusion criteria evaluating the safety of immunomodulators among elderly patients with IBD. Further studies are needed to define the safety of medications among elderly patients with IBD. No association was found in the rate of surgery for hospitalized elderly IBD patients. Among elderly patients with UC, there were decreasing surgery rates with increasing age, whereas no association was found in CD elderly patients. No association was found in length of stay, higher hospitalization costs, or increased postoperative stay in both hospitalized elderly CD and UC patients. Increased postoperative cardiovascular and pulmonary complications were found with increasing age. As a systematic review, the observations of this study may be affected by the limitations of the individual studies and potential publication bias of negative studies. The retrospective nature of the majority of studies may have resulted in selection bias involving surgical or medication bias based on disease severity. Selection bias based on age may also influence the observed outcomes in the included studies. The majority of studies included were conducted in the United States; however, non-English language studies were included in the search strategy. Pooling data from different studies were not possible due to heterogeneity in study design, differing definitions of elderly, and low number of CD studies. Furthermore, the generalizability of these findings is limited by the differences in physiologic and chronologic age. Definitions of age in the included studies included only chronologic age; however, physiologic age likely plays a more important factor in predicting outcomes and function after surgery. This study also has specific strengths; we followed established guidelines for the performance of a systematic review, used specific, pre-

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defined search criteria, and hand-searched included studies and relevant review articles for additional references. To our knowledge, this is the first systematic review of medical and surgical complications among elderly patients with IBD. In conclusion, we performed a systematic review of medical and surgical complications among elderly patients with IBD. Elderly patients undergoing IPAA had similar daytime bowel function and overall pouch failure rates, but studies also noted a small but statistically significant increase in nocturnal bowel movements and nocturnal bowel incontinence at 3 years post-IPAA. We observed a consistent association between elderly age and increased hospital-related infection and all-cause mortality. The included studies suggest an increased risk of infection related to anti-TNFs in elderly IBD patients. While the strengths of our conclusions are limited by the paucity of high-quality studies, we highlight particular areas in need of further research among elderly patients with IBD: medication safety, endoscopic complications, hospitalrelated mortality, and surgical outcomes. Acknowledgments The research reported here was supported in part by the VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (#CIN 13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX. Conflict of interest

None.

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Medical and surgical complications of inflammatory bowel disease in the elderly: a systematic review.

The complications of therapy, hospitalization, and surgery related to inflammatory bowel disease (IBD) in the elderly are not well described. While mu...
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