Two Days Versus Five Days of Postoperative Antibiotics for Complex Appendicitis: Cost Analysis of a Randomized, Noninferiority Trial.

OBJECTIVE: To compare costs for 2 days versus 5 days of postoperative antibiotics within the antibiotics after an aPPendectomy In Complex appendicitis trial.Background:Recent studies suggest that restrictive antibiotic use leads to a significant reduction in hospital stays without compromising patient safety. Its potential effect on societal costs remains underexplored. METHODS: This was a pragmatic, open-label, multicenter clinical trial powered for noninferiority. Patients with complex appendicitis (age ≥ 8 years) were randomly allocated to 2 days or 5 days of intravenous antibiotics after appendectomy. Patient inclusion lasted from June 2017 to June 2021 in 15 Dutch hospitals. The final follow-up was on September 1, 2021. The primary trial endpoint was a composite endpoint of infectious complications and mortality within 90 days. In the present study, the main outcome measures were overall societal costs (comprising direct health care costs and costs related to productivity loss) and cost-effectiveness. Direct health care costs were recorded based on data in the electronic patient files, complemented by a telephone follow-up at 90 days. In addition, data on loss of productivity were acquired through the validated Productivity Cost Questionnaire at 4 weeks after surgery. Cost estimates were based on prices for the year 2019. RESULTS: In total, 1005 patients were evaluated in the "intention-to-treat" analysis: 502 patients were allocated to the 2-day group and 503 to the 5-day group. The mean difference in overall societal costs was - €625 (95% CI: -€ 958 to -€ 278) to the advantage of the 2-day group. This difference was largely explained by reduced hospital stay. Productivity losses were similar between the study groups. Restricting postoperative antibiotics to 2 days was cost-effective, with estimated cost savings of €31,117 per additional infectious complication. CONCLUSIONS: Two days of postoperative antibiotics for complex appendicitis results in a statistically significant and relevant cost reduction, as compared with 5 days. Findings apply to laparoscopic appendectomy in a well-resourced health care setting.

2 days versus 5 days of postoperative antibiotics for complex appendicitis: a pragmatic, open-label, multicentre, non-inferiority randomised trial.

BACKGROUND: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. METHODS: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. FINDINGS: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI -1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. INTERPRETATION: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. FUNDING: The Netherlands Organization for Health Research and Development.

Incisional Hernia Cannot Be Diagnosed by a Patient-Reported Diagnostic Questionnaire.

BACKGROUND: Incisional hernia (IH) is one of the most frequent complications after abdominal surgery. Follow-up with regard to IH remains challenging. Physical examination and imaging to diagnose IH are time-consuming and costly, require devotion of both the physician and patient, and are often not prioritized. Therefore, a patient-reported diagnostic questionnaire for the diagnosis of IH was developed. Objective of this study was to validate this questionnaire in a consecutive sample of patients. METHODS: All patients above 18 y of age who underwent abdominal surgery with a midline incision at least 12 mo ago were eligible for inclusion. Included patients visited the outpatient clinic where they filled out the diagnostic questionnaire and underwent physical examination. The questionnaire answers were compared with the physical examination results. The diagnostic accuracy of the entire questionnaire was assessed by multivariable logistic regression. RESULTS: In total, 241 patients visited the outpatient clinic prospectively. 54 (22%) patients were diagnosed with IH during physical examination. The area under the receiver operating characteristic curve of the diagnostic questionnaire was 0.82. Sensitivity and specificity were respectively 81.5% and 77.5%. The positive and negative predictive values were 51.2% and 94%, respectively. Ten (19%) patients with IH were missed by the questionnaire. CONCLUSIONS: The patient-reported diagnostic questionnaire as currently proposed cannot be used to diagnose IH. However, given the high negative predictive value, the questionnaire might be used to rule out an IH. Long-term follow-up for the diagnosis of IH should be performed by clinical examination.

Zinc-Impregnated Mesh for Abdominal Wall Repair Reduces Infection in a Rat Model of Peritonitis.

BACKGROUND: The objective of this study was to assess whether a zinc-impregnated polypropylene mesh (ZnMesh) has better antibacterial properties in a contaminated environment compared with a regular polypropylene mesh. MATERIALS AND METHODS: Thirty-eight Wistar Han rats underwent cecal ligation and puncture to induce peritonitis 24 h before implantation of an intraperitoneal ZnMesh or a regular polypropylene mesh. Primary outcome was the number of colony forming units (CFU) per sample (mesh and abdominal wall). Secondary outcomes were macroscopic (incorporation of mesh, abscesses, and adhesions on mesh surface) and histological (inflammatory cell reaction, mesh-specific parameters, and collagen deposition) parameters. All outcomes were evaluated after 30 and 90 d. RESULTS: After 30 d, no significant difference in CFU per sample was present between the ZnMesh and control groups. After 90 d, a lower number of CFU per sample was present in the ZnMesh group compared with the control group (trypticase soy agar with 5% sheep blood: 0 log10 CFU/sample IQR: 0-1.40 versus 1.58 log10 CFU/sample IQR: 0-4.30, P = 0.012; MacConkey: 0 log10 CFU/sample IQR: 0-2.65 versus 1.18 log10 CFU/sample IQR: 0-4.04, P = 0.438). After 90 d, the percentage of adhesions on mesh surface was significantly higher in the ZnMesh group (95% IQR: 60%-100% versus 50% IQR: 23%-75%, P = 0.029). No differences were seen in other macroscopic outcomes or histology. CONCLUSIONS: A significantly lower number of CFU per sample was found in the ZnMesh group after 90 d. After 30 d, no statistically significant differences in CFU per sample were seen. This result suggests that the ZnMesh group has better antibacterial properties in a contaminated environment. However, this is at the cost of a significantly higher percentage of adhesions.

Resorbable Synthetic Meshes for Abdominal Wall Defects in Preclinical Setting: A Literature Review.

BACKGROUND: Prosthetic materials for the repair of abdominal wall defects have been studied extensively to improve outcome. A new approach can be the use of a slowly resorbable synthetic mesh, which aims to combine advantages of both synthetic and biological meshes. The objective of this review is to give an overview of the physicochemical characteristics and biomechanical, histological, and macroscopic outcome (recurrence, adhesion formation) of the use of resorbable synthetic meshes, for treatment and prevention of abdominal wall hernias, based on experimental studies. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only experimental studies were included. Outcome parameters were resorption, degradation, organization of connective tissue, inflammatory response, tensile strength, and amount of adhesion formation. Surgical characteristics were taken into account as well (type of defect, clean versus contaminated model, position mesh, repair of the defect, recurrences). RESULTS: In total, eleven articles were included. Three absorbable synthetic meshes are currently available: GORE BIO-A mesh (Gore), TIGR Matrix Surgical mesh (Novus Scientific), and Phasix mesh (Bard). Two studies concluded that, despite an early transient inflammatory reaction in the first months, remodeling was good in GORE BIO-A, 6-12 mo after augmentation or suture line reinforcement with only minimal to moderate adhesions when used intraperitoneally. The TIGR Matrix Surgical mesh shows only partial remodeling with a persistent foreign body reaction after 1 y. Phasix mesh seems to perform well in extraperitoneal implantation after 1 y in two studies, although the defect was small. Only two studies directly compared two resorbable synthetic meshes under the same circumstances. The latter also included a number of animals where the meshes were used in a contaminated nonhernia model. No hernia recurrences or deaths of animals were described in all studies. CONCLUSIONS: The use of resorbable synthetic meshes in the prevention or treatment of abdominal wall defects in animal experiments with small defects in clean setting seems safe, with no serious complications related to the device during short-term follow-up. However, there is no evidence available that can support the advantages of resorbable synthetic meshes over the use of synthetic or biological meshes, mostly due to lack of good data. More experimental studies are needed, followed by randomized controlled trials and prospective registries in humans with a sufficiently long follow-up period, to reveal the potential advantages in clinical practice.

Non-Cross-Linked Collagen Mesh Performs Best in a Physiologic, Noncontaminated Rat Model.

BACKGROUND: In laparoscopic incisional hernia repair, direct contact between the prosthesis and abdominal viscera is inevitable and may lead to adhesions. Despite the large variety of mesh prosthesis, little is known about their in vivo behavior. Biological meshes are considered to have many advantages, but due to their price they are rarely used. A rat model was used to assess biological and conventional synthetic meshes on their in vivo characteristics. DESIGN: One-hundred twenty male Wistar rats were randomized into five groups of 24 rats. A mesh was implanted intraperitoneally and fixated with nonresorbable sutures. The following five meshes were implanted: Parietene (polypropylene), Permacol (cross-linked porcine acellular dermal matrix), Strattice (non-cross-linked porcine acellular dermal matrix), XCM Biologic (non-cross-linked porcine acellular dermal matrix), and Omyra Mesh (condensed polytetrafluoroethylene). The rats were sacrificed after 30, 90, or 180 days. Incorporation, shrinkage, adhesions, abscess formation, and histology were assessed for all meshes. RESULTS: All animals thrived postoperatively. After 180 days, Permacol, Parietene, and Omyra Mesh had a significantly better incorporation than Strattice ( P = .001, P = .019, and P = .037 respectively). After 180 days, Strattice had significantly fewer adhesions on the surface of the mesh than Parietene ( P < .001), Omyra Mesh ( P = .011), and Permacol ( P = .027). After 30 days, Permacol had significantly stronger adhesions than Strattice ( P = .030). However, this difference was not significant anymore after 180 days. After 180 days, there was significantly less shrinkage in Permacol than in Strattice ( P = .001) and Omyra Mesh ( P = .050). CONCLUSION: Based on incorporation, adhesions, mesh shrinkage, and histologic parameters, Strattice performed best in this experimental rat model.

Prevention of incisional hernia with prophylactic onlay and sublay mesh reinforcement versus primary suture only in midline laparotomies (PRIMA): 2-year follow-up of a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Incisional hernia is a frequent long-term complication after abdominal surgery, with a prevalence greater than 30% in high-risk groups. The aim of the PRIMA trial was to evaluate the effectiveness of mesh reinforcement in high-risk patients, to prevent incisional hernia. METHODS: We did a multicentre, double-blind, randomised controlled trial at 11 hospitals in Austria, Germany, and the Netherlands. We included patients aged 18 years or older who were undergoing elective midline laparotomy and had either an abdominal aortic aneurysm or a body-mass index (BMI) of 27 kg/m2 or higher. We randomly assigned participants using a computer-generated randomisation sequence to one of three treatment groups: primary suture; onlay mesh reinforcement; or sublay mesh reinforcement. The primary endpoint was incidence of incisional hernia during 2 years of follow-up, analysed by intention to treat. Adjusted odds ratios (ORs) were estimated by logistic regression. This trial is registered at ClinicalTrials.gov, number NCT00761475. FINDINGS: Between March, 2009, and December, 2012, 498 patients were enrolled to the study, of whom 18 were excluded before randomisation. Therefore, we included 480 patients in the primary analysis: 107 were assigned primary suture only, 188 were allocated onlay mesh reinforcement, and 185 were assigned sublay mesh reinforcement. 92 patients were identified with an incisional hernia, 33 (30%) who were allocated primary suture only, 25 (13%) who were assigned onlay mesh reinforcement, and 34 (18%) who were assigned sublay mesh reinforcement (onlay mesh reinforcement vs primary suture, OR 0·37, 95% CI 0·20-0·69; p=0·0016; sublay mesh reinforcement vs primary suture, 0·55, 0·30-1·00; p=0·05). Seromas were more frequent in patients allocated onlay mesh reinforcement (34 of 188) than in those assigned primary suture (five of 107; p=0·002) or sublay mesh reinforcement (13 of 185; p=0·002). The incidence of wound infection did not differ between treatment groups (14 of 107 primary suture; 25 of 188 onlay mesh reinforcement; and 19 of 185 sublay mesh reinforcement). INTERPRETATION: A significant reduction in incidence of incisional hernia was achieved with onlay mesh reinforcement compared with sublay mesh reinforcement and primary suture only. Onlay mesh reinforcement has the potential to become the standard treatment for high-risk patients undergoing midline laparotomy. FUNDING: Baxter; B Braun Surgical SA.

Small bites versus large bites for closure of abdominal midline incisions (STITCH): a double-blind, multicentre, randomised controlled trial.

BACKGROUND: Incisional hernia is a frequent complication of midline laparotomy and is associated with high morbidity, decreased quality of life, and high costs. We aimed to compare the large bites suture technique with the small bites technique for fascial closure of midline laparotomy incisions. METHODS: We did this prospective, multicentre, double-blind, randomised controlled trial at surgical and gynaecological departments in ten hospitals in the Netherlands. Patients aged 18 years or older who were scheduled to undergo elective abdominal surgery with midline laparotomy were randomly assigned (1:1), via a computer-generated randomisation sequence, to receive small tissue bites of 5 mm every 5 mm or large bites of 1 cm every 1 cm. Randomisation was stratified by centre and between surgeons and residents with a minimisation procedure to ensure balanced allocation. Patients and study investigators were masked to group allocation. The primary outcome was the occurrence of incisional hernia; we postulated a reduced incidence in the small bites group. We analysed patients by intention to treat. This trial is registered at Clinicaltrials.gov, number NCT01132209 and with the Nederlands Trial Register, number NTR2052. FINDINGS: Between Oct 20, 2009, and March 12, 2012, we randomly assigned 560 patients to the large bites group (n=284) or the small bites group (n=276). Follow-up ended on Aug 30, 2013; 545 (97%) patients completed follow-up and were included in the primary outcome analysis. Patients in the small bites group had fascial closures sutured with more stitches than those in the large bites group (mean number of stitches 45 [SD 12] vs 25 [10]; p<0·0001), a higher ratio of suture length to wound length (5·0 [1·5] vs 4·3 [1·4]; p<0·0001) and a longer closure time (14 [6] vs 10 [4] min; p<0·0001). At 1 year follow-up, 57 (21%) of 277 patients in the large bites group and 35 (13%) of 268 patients in the small bites group had incisional hernia (p=0·0220, covariate adjusted odds ratio 0·52, 95% CI 0·31-0·87; p=0·0131). Rates of adverse events did not differ significantly between groups. INTERPRETATION: Our findings show that the small bites suture technique is more effective than the traditional large bites technique for prevention of incisional hernia in midline incisions and is not associated with a higher rate of adverse events. The small bites technique should become the standard closure technique for midline incisions. FUNDING: Erasmus University Medical Center and Ethicon.

Patient reported outcome measurements in the diagnosis of incisional hernia: PROMIS questionnaire, a pilot study.

BACKGROUND: Incisional hernia (IH) is the most frequent complication after abdominal surgery. Long-term follow-up is crucial. Patient-reported outcome measurements (PROMs) are able to monitor patients' disease progression after treatment. Until now, there are no PROMs that assess patients after abdominal surgery or that detects patients with IH. We aimed to develop a reliable questionnaire to assist in diagnosing IH, called the "PROMIS questionnaire": Patient-Reported Outcome Measurements in the Diagnosis of Incisional Hernias. In this pilot study, the reliability of this questionnaire is being determined. METHODS: Patients diagnosed with IH between 2013 and 2014 were included. A questionnaire with seven questions was developed. Patients were asked whether they thought they had IH, whether they felt any pain at the site of the scar, and whether they saw or felt a lump or a bulge. Furthermore, smoking history and patients' weight and height were taken into account. Patients were approached three times by telephone, with an interval of 1 week. Test-retest reliability, internal consistency, and sensitivity were measured. RESULTS: Forty-three patients were included. Test-retest reliability was 1.0, and internal consistency was 0.56. The question regarding patients' pain was least consistent with other questions. The overall sensitivity of the questionnaire was 95%. CONCLUSIONS: The PROMIS questionnaire is a highly reliable questionnaire, but the internal consistency is modest. The clinical relevancy of pain in IH patients is essential. Therefore, this question will be kept in the current PROMIS questionnaire. It needs further validation in a prospective cohort study, to use it as a diagnostic tool in the future to detect IH.

Outcomes of a new slowly resorbable biosynthetic mesh (Phasix™) in potentially contaminated incisional hernias: A prospective, multi-center, single-arm trial.

BACKGROUND: Resorbable biomaterials have been developed to reduce the amount of foreign material remaining in the body after hernia repair over the long-term. However, on the short-term, these resorbable materials should render acceptable results with regard to complications, infections, and reoperations to be considered for repair. Additionally, the rate of resorption should not be any faster than collagen deposition and maturation; leading to early hernia recurrence. Therefore, the objective of this study was to collect data on the short-term performance of a new resorbable biosynthetic mesh (Phasix™) in patients requiring Ventral Hernia Working Group (VHWG) Grade 3 midline incisional hernia repair. MATERIALS AND METHODS: A prospective, multi-center, single-arm trial was conducted at surgical departments in 15 hospitals across Europe. Patients aged ≥18, scheduled to undergo elective Ventral Hernia Working Group Grade 3 hernia repair of a hernia larger than 10 cm2 were included. Hernia repair was performed with Phasix™ Mesh in sublay position when achievable. The primary outcome was the rate of surgical site occurrence (SSO), including infections, that required intervention until 3 months after repair. RESULTS: In total, 84 patients were treated with Phasix™ Mesh. Twenty-two patients (26.2%) developed 32 surgical site occurrences. These included 11 surgical site infections, 9 wound dehiscences, 7 seromas, 2 hematomas, 2 skin necroses, and 1 fistula. No significant differences in surgical site occurrence development were found between groups repaired with or without component separation technique, and between clean-contaminated or contaminated wound sites. At three months, there were no hernia recurrences. CONCLUSION: Phasix™ Mesh demonstrated acceptable postoperative surgical site occurrence rates in patients with a Ventral Hernia Working Group Grade 3 hernia. Longer follow-up is needed to evaluate the recurrence rate and the effects on quality of life. This study is ongoing through 24 months of follow-up.