Appendicitis: Rural Patient Status is Associated with

Appendicitis: Rural Patient Status is Associated with Increased Duration of Prehospital Symptoms and Worse Outcomes in High- and Low-MiddleIncome Countries Matthew C. Hernandez, Eric Finnesgaard, Johnathon M. Aho, Victor Y. Kong, John L. Bruce, Stephanie F. Polites, Grant L. Laing, et al. World Journal of Surgery Official Journal of the International Society of Surgery/Société Internationale de Chirurgie ISSN 0364-2313 World J Surg DOI 10.1007/s00268-017-4344-5

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Author's personal copy World J Surg DOI 10.1007/s00268-017-4344-5

ORIGINAL SCIENTIFIC REPORT

Appendicitis: Rural Patient Status is Associated with Increased Duration of Prehospital Symptoms and Worse Outcomes in Highand Low-Middle-Income Countries Matthew C. Hernandez1 • Eric Finnesgaard4 • Johnathon M. Aho1,3 • Victor Y. Kong2 • John L. Bruce2 • Stephanie F. Polites1 • Grant L. Laing2 Damian L. Clarke2 • Martin D. Zielinski1

•

Ó Socie´te´ Internationale de Chirurgie 2017

Abstract Introduction Appendicitis is a significant economic and healthcare burden in low-, middle-, and high-income countries. We aimed to determine whether urban and rural patient status would affect outcomes in appendicitis in a combined population regardless of country of economic status. We hypothesize that patients from rural areas and both high- and low-middle-income countries would have disproportionate outcomes and duration of symptoms compared to their urban counterparts. Methods Adults (C18 years) with appendicitis during 2010–2016 in South Africa and USA were reviewed using multi-institutional data. Baseline demographic, operative details, durations of stay, and complications (Clavien– Dindo index) were collected. AAST grades were assigned by two independent reviewers based on operative findings. Summary, univariate, and multivariable analyses of rural and urban patients in both countries were performed. Results There were 2602 patients with a median interquartile range [IQR] of 26 [18–40] years; 45% were female. Initial management included McBurney incisions (n = 458, 18%), laparotomy (n = 915, 35%), laparoscopic appendectomy (n = 1185, 45%), and laparoscopy converted to laparotomy (n = 44, 2%). Comparing rural versus urban patient status, there were increased overall median [IQR] AAST grades (3 [1–5] vs. 2 [1–3], p = 0.001), prehospital duration of symptoms (2 [1–5] vs. 2 [1–3], p = 0.001), complications (44.3 vs. 23%, p = 0.001), and need for temporary abdominal closure (20.3 vs. 6.9%, p = 0.001). Conclusion Despite socioeconomic status and country of origin, patients from more rural environments demonstrate poorer outcomes notwithstanding significant differences in overall disease severity. The AAST grading system may serve a potential benchmark to recognize areas with disparate disease burdens. This information could be used for strategic improvements for surgeon placement and availability.

Oral presentation, World Congress of Surgery, 2017, Basel, Switzerland. & Matthew C. Hernandez [email protected]

Stephanie F. Polites [email protected]

Johnathon M. Aho [email protected]

Grant L. Laing [email protected]

Victor Y. Kong [email protected]

Damian L. Clarke [email protected]

John L. Bruce [email protected]

Martin D. Zielinski [email protected]

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Author's personal copy World J Surg

Introduction Acute appendicitis is a common abdominal emergency which can be cured by definitive surgery [1]. Appendectomy can be performed safely and effectively by most surgeons with an appropriate level of training and in critical access facilities [2]. Despite this, the disease continues to be associated with significant morbidity and even mortality, especially in developing countries [3, 4]. The risk of an adverse outcome increases as the severity of the disease process increases [5]. The most common factor associated with increasing severity of disease is delay to care and delay to surgery [6]. For this reason, there is a great deal of interest in examining factors which contribute to these delays. Lack of access to appropriate health care is believed to be a major contributing factor to delay in surgical patients in general and in acute appendicitis in particular [7]. The Lancet Commission for Global Surgery has drawn attention to the fact that major parts of the world and of the global population cannot access safe and effective surgical care [8, 9]. This lack of access is not uniform, and differences in access exist both between countries and within countries, regardless of the overall economic classification of the country [10–12]. A number of studies have reviewed the relationship between whether a patient resides in a rural or an urban area, and the severity and outcome of acute appendicitis [13, 14]. However, most of these reports have focused on intra-country differences and used a simple binary classification of grade of disease, to categorize the severity of the pathology [7]. This study compares differences in outcome between urban and rural patients with acute appendicitis from a high-income country (HIC), namely the USA, and from a low-middle-income country (LMIC), namely South Africa. It makes use of the newly introduced and recently validated, American Association for the Surgery of Trauma (AAST) disease severity scoring system, to grade the severity of the disease [15]. This score has been validated in both HIC and LMIC for adult patients with appendicitis [16, 17]. We hypothesized that rural patients would demonstrate increased disease severity and poorer 1

Division of Trauma Critical Care and General Surgery, Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA

2

Department of Surgery, Pietermaritzburg Metropolitan Hospital Complex, University of KwaZulu-Natal, Durban, South Africa

3

Biomedical Engineering and Physiology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

4

Mayo Medical School, Mayo Clinic College of Medicine, Rochester, MN 55905, USA

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outcomes compared to urban patients in both the HIC and LMIC safter stratification using the AAST EGS grade for appendicitis.

Methods This was a retrospective multi-institution cohort study undertaken by the authors. Institutional Review Board approval was obtained prior to conducting the study from both the Mayo Clinic and the Biomedical Research Committee (BREC) of the University of KwaZulu-Natal. Databases were retrospectively queried at each institution for the period 2010–2016. The USA was considered a highincome country (HIC), and South Africa was considered a low-middle-income country (LMIC). Patient cohort Baseline demographic information, prehospital symptom duration, physiologic and laboratory data, operation approach (midline laparotomy, limited incision, and laparoscopy), complication types and rates, according to definitions determined by the National Surgical Quality Improvement Program (NSQIP) [18], complication severity and subsequent interventions as graded by the Clavien– Dindo index [19], relaparotomy rate, temporary abdominal closure utilization, patient referral location (rural vs. urban), total duration of hospital stay, and 30-day mortality were abstracted. Rural–urban definition For patients that presented to the Mayo Clinic in Rochester, MN rural versus urban patient status was assigned using residential influence codes provided by U.S. Department of Agriculture [20]. Patients’ home address was then queried in the electronic medical record to determine their county location. In order to further quantify the differences in rural versus urban residential status, the distance in miles from the Mayo Clinic was calculated and utilized for the sole purpose of ascertaining distance and disease severity. Pietermaritzburg is the largest city and capital of KwaZulu-Natal (KZN) Province in South Africa. The city has a population of one million people and is served by the hospitals of the Pietermaritzburg Metropolitan Complex. This complex also drains the deep rural areas of Western KwaZulu-Natal. This area has a population of approximately two million. All referrals to the Pietermaritzburg Complex from outside the city of Pietermaritzburg are from rural institutions.


AAST grade assignment The AAST grade for appendicitis is depicted in Fig. 1 and Table 1. This grading scale assigns disease severity based on increasing anatomic injury, similar to the Organ Injury Scale, which is a well-validated method to assign severity in trauma. The grade contains five levels of increasing disease severity related to various extents of perforation and surrounding tissue/organ inflammation and involvement. AAST grades represent following types of anatomic injury grade I (acute inflammation), grade II (suppuration), grade III (perforation), grade IV (perforation with abscess and/or phlegmon), and grade V (perforation with feculent peritonitis). Two reviewers (EJF and VYK) retrospectively assigned AAST grade to patients’ operative findings, and a third reviewer (MCH) adjudicated any discrepancies. The AAST grade was assigned based on operative criteria designated in Fig. 1. All analyses comparing outcomes were assessed using the final AAST grade. Primary outcome The primary outcome was complication severity, as defined by Clavien and Dindo, between rural and urban patients in both HIC and LMIC. Secondary outcomes Secondary outcomes included hospital duration of stay, development of any complication as defined by the NSQIP complication variables, relaparotomy rate, postoperative pneumonia, acute kidney injury (defined as a threefold rise in creatinine from baseline), temporary abdominal closure rate, and 30-day mortality. Statistical analyses Univariate analyses to assess the relationship of AAST grade, clinical outcomes, and the effect of patient residential status (rural vs. urban) were performed using twotailed t tests for normally distributed data and Wilcoxon rank sum for non-normally distributed data. All continuous variables were described using means with standard deviations (SD) if normally distributed and medians with interquartile ranges if gross skewness was present. Categorical variables were summarized as proportions and assessed using Chi-square tests. Variables on univariate analyses with p \ 0.05 were included in a multivariable logistic regression analysis in order to determine risk factors predictive for the development of postoperative complication using odds ratios with 95% confidence intervals (CI). All data analyses were performed using JMP (SAS Institute, Inc. Cary, NC). GraphPad Prism (GraphPad

Software, Inc. La Jolla CA) was utilized for all visual graphics.

Results Overall patient characteristics and outcomes A total of 2602 patients were reviewed during the study period. The median [IQR] age in years for the population was 26 [18–40], and 45% were female. The overall median [IQR] duration of prehospital symptoms was 2 [1–4] days. There were 1220 (47%) patients that presented from a rural environment in both the HIC and LMIC. All patients underwent an operative intervention. Overall, the AAST grade (n, %) was normal (10, 0.4%), AAST I (994, 38.2%), AAST II (499, 19.2%), AAST III (284, 11%), AAST IV (229, 8.2%), AAST V (586, 23%). Operative management (n, %) included McBurney’s incision (458, 18%), laparoscopic appendectomy (1185, 45%), midline laparotomy (915, 35%), and laparoscopic converted to laparotomy (44, 2%). Nearly one-third of patients (n = 879) experienced a complication as defined by NSQIP. Overall, complication rates for each AAST grade were AAST I (8.8%), AAST II (11.8%), AAST III (34.1%), AAST IV (50.7%), and AAST V (86%). The overall utilization of temporary abdominal closure was 14%, and there was a relaparotomy rate of 21%. The median [IQR] overall duration of stay for patients was 2 [1–6] days. The 30-day mortality was 0.9% (n = 25). Rural versus urban patient status Comparison of the patient characteristics using the rural and urban status for both HIC and LMIC is outlined in Tables 2 and 3. This demonstrated no differences in age, preoperative temperature, white blood cell count, and heart rate between rural and urban patients within both countries. There was a similar median [IQR] prehospital duration of symptoms in both rural and urban patients in the HIC (1 [1–2] vs. 1 [1–2], p = 0.55). Conversely, the prehospital median [IQR] symptom duration was increased in rural compared to urban patients within the LMIC (5 [3–7] vs. 2 [1–4], p = 0.001). In the HIC, the majority of disease severity was AAST grades I and II indicating less severe disease, whereas in the LMIC there was increased frequency of AAST grades (III–V). Further univariate analysis revealed parallels between rural and urban patient residential status in both countries. Rural HIC patients demonstrated significantly increased median [IQR] AAST appendicitis disease severity compared to urban HIC patients (3 [1–4] vs. 1 [1–1], p = 0.001). Similarly, in the LMIC, rural patients

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Fig. 1 American Association for the Surgery of Trauma Emergency General Surgery Grade for Appendicitis Table 1 American Association for the Surgery on Trauma Grading System for Anatomic Severity of Disease Grade

Image AAST (I-AAST) description of organ

Operative AAST description of appendicitis

Normal

Normal appearance, appendix not visualized without any other abnormality

Normal appendix

Grade I Grade II

Appendiceal thickening [6 mm with mild periappendiceal edema Appendiceal thickening [6 mm with severe periappendiceal edema

Acutely inflamed appendix, intact Gangrenous appendix, intact

Grade III

Appendiceal thickening [6 mm, severe periappendiceal thickening with free intraperitoneal fluid in the right lower quadrant/pelvis

Perforated appendix with local contamination

Grade IV Grade V

Appendiceal thickening [6 mm or non-visualized appendix with abscess or phlegmon

Perforated appendix with periappendiceal phlegmon or abscess Perforated appendix with generalized peritonitis

Appendiceal thickening [6 mm or non-visualized appendix with free intraperitoneal fluid [1 quadrant

display higher-median [IQR] AAST grade than urban patients (5 [3–5] vs. 2 [2–4], p = 0.001). Operative approach was increasingly more invasive for rural compared to urban patients in both the HIC and LMIC. In the HIC, rural patients underwent less laparoscopy for appendicitis compared to urban patients (46.2 vs. 54%, p = 0.02), increased McBurney’s incision (5.8 vs. 3%, p = 0.02), as well as increased conversion from laparoscopy to laparotomy (2.7 vs. 1%, p = 0.004). Likewise, for rural and urban patients in the LMIC there were significant differences in the rates of laparoscopy (3.3 vs. 5.9%, p = 0.02) and McBurney’s incision (20.5 vs. 50.4%, p = 0.001). The rates of temporary abdominal closure in the HIC were increased but not statistically significant in the rural compared to urban population (1.3 vs. 0.6%, p = 0.9). Interestingly, there was a demonstrable difference in the utilization of this therapy in the rural LMIC patients compared to urban (30.6 vs. 10%, p = 0.001).

rural patients in both the HIC and LMIC. Figure 2 demonstrates that there was an increased burden of Clavien–Dindo complication severity in rural patients compared to urban patients in a HIC. Similarly, Fig. 3 demonstrates a similar finding for the rural compared to urban patients in the LMIC. The median [IQR] duration of stay was increased for rural patients compared to urban patients both in the LMIC (4 [2–7] vs. 2 [2–3], p = 0.001) and in the HIC (2 [0–3] vs. 1 [0–1], p = 0.005). On regression, factors that were independently associated (p \ 0.05) with the development of any complication included (odds ratio (95% CI)), AAST grade (reference grade I), AAST grade II 2.05 (1.02–3.5), AAST grade III 3.4 (2.7–4.8), AAST grade IV 5.5 (3.8–6.3), AAST grade V 13.7 (6.6–23.1), rural patient status 2.1 (1.5–3.1), and tachycardia ([110 bpm) 1.6 (1.1–2.3).

Discussion Postoperative outcomes Overall outcomes between the HIC and LMIC by patient referral status are outlined in Table 4. There were similarities in the degree of the severity of complications in

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The successful management of acute appendicitis requires early and accurate diagnosis and the efficacious management of the disease [21, 22]. Appendicitis is a high-volume disease, and as such it has the potential to provide a model

Author's personal copy World J Surg Table 2 Patient characteristics from a HIC for appendicitis; values are reported as median [interquartile range] or medians unless otherwise noted Variables

AAST grade I

II

III

IV

V

Rural N = 303

Urban N = 444

Rural N = 121

Urban N = 98

Rural N = 74

Urban N = 52

Rural N = 30

Urban N = 20

Rural N = 29

Urban N = 16

Female %

46.5

51.8

43

36.7

36.5

34.6

40

55

34.5

31.2

Age [IQR] (years)

34 [24–51]

32 [25–44]

40 [25–57]

44 [31–55]

55 [35–71]

55 [39–62]

55 [39–64]

53 [34–67]

62 [46–75]

54 [34–37]

Characteristics

Clinical presentation Duration of preoperative abdominal pain (days)

1

1

2

1

3

2

2

1

3

2

Admission temperature (°C)

36.8

36.8

36.8

36.8

36.8

36.8

37.1

36.9

37.2

36.9

Heart rate (bpm)

82

82

84

80

90

85

95

89

93

90

White blood cell count (9 109/L)

13

12.8

13.3

12.7

14.5

13

13.2

12.4

16.7

14.4

Laparoscopy or McBurney incision (n, %)

300, 98.7

427, 96.6

116, 95.9

93, 95

48, 86.6

92.4

21, 69.7

18, 90

13, 44

11, 74

Midline laparotomy (n, %)

2, 0.7

0

0

1, 1

1.3

1, 1.9

2, 7

1, 5

7, 25

3, 14

Conversion (n, %)

1, 0.6

17, 0.4

5, 4.1

4, 4

12.1

3, 5.7

7, 23.3

1, 5

9, 31

2, 12

Surgical method

to assess and compare surgical healthcare systems [3, 23]. The increased emphasis on providing safe, sustainable, and effective surgical care to global populations, however, requires granular assessment of common surgical diseases in terms of spectrum, severity, and outcome [8]. Although a number of studies have compared outcomes of acute appendicitis based on different patient factors such as income, class, race, geographical location, and socioeconomic status, the lack of an accepted classification for disease severity has tended to limit these analyses [24, 25]. We have shown that the AAST EGS grade for appendicitis allows for a meaningful comparison of severity and outcome between patients with a rural residential status compared to an urban residential status. Our findings have demonstrated poorer outcomes for rural patients relative to urban patients in both the HIC and LMIC. Rural patients, regardless of country of origin, tend to have more severe disease, and this leads to the need for more invasive

operative management strategies and consequently an increased rate and severity of complications as well as longer durations of hospital stay, and increased mortality. Patients defined as urban presented with a lower degree of anatomic severity compared to the rural patients in both HIC and LMIC. One potential explanation for increased disease severity in rural patients is the increased duration of prehospital symptoms [26]. The longer the delay to diagnosis and surgery, the more likely it is that disease severity will increase. In our cohort, rural patients demonstrated increased durations of prehospital symptoms compared to urban patients and this almost certainly translated into more severe AAST grading seen at operation. This was more pronounced in the rural patients from the LMIC compared to those from the HIC. The present study provides granular details regarding the operative approach for patients in both HIC and LMIC. Patients in the HIC overwhelmingly underwent

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Author's personal copy World J Surg Table 3 Patient characteristics from a LMIC for appendicitis; values are reported as median [interquartile range] or medians unless otherwise noted Variables

AAST grade I

II

III

IV

V

Rural N = 93

Urban N = 154

Rural N = 39

Urban N = 241

Rural N = 65

Urban N = 93

Rural N = 90

Urban N = 89

Rural N = 376

Urban N = 165

Female %

41

44

31

34

46

30

33

40

63

35

Age [IQR] (years)

22 [17–28]

19 [18–22]

22 [19–23]

24 [19–27]

23 [20–27]

25 [21–29]

20 [18–23]

22 [20–31]

20 [18–22]

25 [19–34]

Characteristics

Clinical presentation Duration of preoperative abdominal pain (days)

2

2

3

2

4

3

4

3

5

3

Admission temperature (°C)

37

36.8

37

37

37.3

36.9

37.8

37.1

38.1

37.6

Heart rate (bpm)

86

84

96

90

105

100

101

98

122

112

White blood cell count (9 109/L)

13.2

11.8

14.2

13.3

14.6

13.8

16.1

15

17.2

16

Laparoscopy or McBurney incision (n, %)

77, 82.8

139, 90

34, 87.4

212, 87.6

17, 25

16, 17.2

5, 6

11, 12

8, 2

3, 2

Midline laparotomy (n, %)

14, 15.2

15, 10

5, 12.8

29, 2.4

48, 75

77, 82.8

85, 94

78, 88

368, 98

162, 98

Conversion (n, %)

2, 2

0

0

0

0

0

0

0

0

0

Surgical method

laparoscopic appendectomy compared to the LMIC. Although this suggests restricted access to laparoscopic surgery in the LMIC, more advanced disease is less likely to be suitable for a laparoscopic approach. Despite the high rate of laparoscopy offered to patients in the HIC, those with rural status displayed increased rates of conversion to laparotomy, midline laparotomy, and open abdomen therapy, compared to their urban counterparts. Likewise, the small percentage of patients which underwent laparoscopy in the LMIC all had low-grade disease severity (AAST grade I) and were urban in origin. Previous analyses have also shown this trend of an increased need for more invasive and open procedures amongst rural patients. Since previous analyses utilized a more broad definition of disease severity or used or aggregate billing data, they struggled to clearly show an association between rural and urban patient status and disease severity and subsequent morbidity [7]. Documenting disease severity, according to

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the AAST EGS grade, is a more objective method to assess disease severity. Our previous work demonstrated the internal and external validity of this method and suggested that the AAST appendicitis grade is broadly generalizable to a global population [16, 17]. Our previous work demonstrated that the AAST EGS grade for appendicitis demonstrated validity and was associated with several outcomes including complication severity, duration of hospital stay, and mortality [16]. Further, in this work we demonstrated that imaging findings correlated well with operative findings. This is unique in that preoperative imaging AAST EGS appendicitis grades also correlated with outcome. To address the generalizability of the method, we applied the AAST EGS appendicitis grade to a population with increasingly severe appendicitis in South Africa. There we demonstrated that increasing disease severity was associated with important clinical outcomes, including the need for relaparotomy [17].

Author's personal copy World J Surg Table 4 (A) Postoperative outcomes in a HIC and (B) LMIC values reported as medians unless otherwise noted Variables

AAST grade I

II

III

IV

V

Rural N = 303

Urban N = 444

Rural N = 121

Urban N = 98

Rural N = 74

Urban N = 52

Rural N = 30

Urban N = 20

Rural N = 29

Urban N = 16

Open abdomen (n, %) Duration of stay

0 1

0 1

2, 1.4 1

0 1

2, 2.9 3

0 2

3, 10.5 5

0 3

3, 11.1 6

1, 5.9 4

Relaparotomy (m, %)

9, 0.3

9, 0.2

5, 4.1

3, 3

3, 3.8

1, 2.7

2, 6.6

1, 5

4, 12.5

2, 10.3

A

Variables

AAST grade I

II

III

IV

V

Rural N = 93

Urban N = 154

Rural N = 39

Urban N = 241

Rural N = 65

Urban N = 93

Rural N = 90

Urban N = 89

Rural N = 376

Urban N = 165

65, 41

B Open abdomen (n, %)

1, 1

0

0

0

2, 3.3

3, 3

6, 7

2, 2

195, 52

Duration of stay

3

2

2

2

7

4

7

5

10

7

Relaparotomy (n, %)

2, 2.1

9, 0.6

1, 1.7

0

7, 11

7, 8

33, 37

20, 22

319, 85

112, 68

Fig. 2 Complication severity in a HIC a rural patients and b urban patients

Fig. 3 Complication severity in a LMIC a rural patients and b urban patients

Strategies to overcome logistical problems associated with managing acute surgical emergencies in rural areas, in both HICs and LMICs, are required. The key to improving these outcomes is earlier recognition and earlier access to surgery. Utilizing the clinical and radiological component of the AAST EGS grade either could potentially improve

triage of acute appendicitis. Strategies to expand access to minimally invasive or non-operative management for rural patients may need to be developed. There are several limitations to our work. This is a retrospective study, and the assignment of disease severity from operative report data is inherently limited. While the

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data input into operative reports may not be entirely reflective disease severity at the time of operation, we have previously demonstrated that this method adequately assesses patients’ anatomic injury severity. Further, we were unable to assess the preoperative impact of the AAST grade and outcomes due to differences in imaging and decision to operate between institutions. Despite this, our application of the AAST to this large patient cohort suggests that rural and urban differences exist for patient outcomes in appendicitis and that these are similar in both HIC and LMIC.

Conclusion Despite socioeconomic status and country of origin, patients from more rural environments demonstrate poorer outcomes notwithstanding significant differences in overall disease severity. The AAST grading system may serve a potential benchmark to recognize areas with disparate disease burdens. This information could be used for strategic improvements for surgeon placement and availability. Compliance with ethical standards Conflict of interest All authors declare that they have no conflict of interest.

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