Laparoscopic cholecystectomy versus conservative management for adults with uncomplicated symptomatic gallstones: the C-GALL RCT.

Background: Gallstone disease is a common gastrointestinal disorder in industrialised societies. The prevalence of gallstones in the adult population is estimated to be approximately 10-15%, and around 80% remain asymptomatic. At present, cholecystectomy is the default option for people with symptomatic gallstone disease. Objectives: To assess the clinical and cost-effectiveness of observation/conservative management compared with laparoscopic cholecystectomy for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones in secondary care. Design: Parallel group, multicentre patient randomised superiority pragmatic trial with up to 24 months follow-up and embedded qualitative research. Within-trial cost-utility and 10-year Markov model analyses. Development of a core outcome set for uncomplicated symptomatic gallstone disease. Setting: Secondary care elective settings. Participants: Adults with symptomatic uncomplicated gallstone disease referred to a secondary care setting were considered for inclusion. Interventions: Participants were randomised 1: 1 at clinic to receive either laparoscopic cholecystectomy or observation/conservative management. Main outcome measures: The primary outcome was quality of life measured by area under the curve over 18 months using the Short Form-36 bodily pain domain. Secondary outcomes included the Otago gallstones' condition-specific questionnaire, Short Form-36 domains (excluding bodily pain), area under the curve over 24 months for Short Form-36 bodily pain domain, persistent symptoms, complications and need for further treatment. No outcomes were blinded to allocation. Results: Between August 2016 and November 2019, 434 participants were randomised (217 in each group) from 20 United Kingdom centres. By 24 months, 64 (29.5%) in the observation/conservative management group and 153 (70.5%) in the laparoscopic cholecystectomy group had received surgery, median time to surgery of 9.0 months (interquartile range, 5.6-15.0) and 4.7 months (interquartile range 2.6-7.9), respectively. At 18 months, the mean Short Form-36 norm-based bodily pain score was 49.4 (standard deviation 11.7) in the observation/conservative management group and 50.4 (standard deviation 11.6) in the laparoscopic cholecystectomy group. The mean area under the curve over 18 months was 46.8 for both groups with no difference: mean difference -0.0, 95% confidence interval (-1.7 to 1.7); p-value 0.996; n = 203 observation/conservative, n = 205 cholecystectomy. There was no evidence of differences in quality of life, complications or need for further treatment at up to 24 months follow-up. Condition-specific quality of life at 24 months favoured cholecystectomy: mean difference 9.0, 95% confidence interval (4.1 to 14.0), p < 0.001 with a similar pattern for the persistent symptoms score. Within-trial cost-utility analysis found observation/conservative management over 24 months was less costly than cholecystectomy (mean difference -£1033). A non-significant quality-adjusted life-year difference of -0.019 favouring cholecystectomy resulted in an incremental cost-effectiveness ratio of £55,235. The Markov model continued to favour observation/conservative management, but some scenarios reversed the findings due to uncertainties in longer-term quality of life. The core outcome set included 11 critically important outcomes from both patients and healthcare professionals. Conclusions: The results suggested that in the short term (up to 24 months) observation/conservative management may be a cost-effective use of National Health Service resources in selected patients, but subsequent surgeries in the randomised groups and differences in quality of life beyond 24 months could reverse this finding. Future research should focus on longer-term follow-up data and identification of the cohort of patients that should be routinely offered surgery. Trial registration: This trial is registered as ISRCTN55215960. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/192/71) and is published in full in Health Technology Assessment; Vol. 28, No. 26. See the NIHR Funding and Awards website for further award information.

The C-GALL study assessed the benefits, in terms of symptoms, quality of life and costs, of cholecystectomy versus observation (conservative management: by the patient and general practitioner that might include dietary advice and pain management and surgery if needed). Four hundred and thirty-four patients with symptomatic gallstones were randomly allocated surgery or conservative management. The main symptom of ongoing bodily pain and some other quality-of-life measures were assessed over the next 2 years using postal questionnaires. After 2 years, 70% of those allocated to surgery had been operated on and 37% of the observation group either had an operation or were waiting for one. There was no difference in bodily pain or overall quality of life between the groups. However, participants in the surgery group reported fewer ongoing problems related to their gallstone disease or after surgery than those in the conservative management group. Surgery was, however, more costly than conservative management. The C-GALL study has shown that for some patients, a conservative management approach may be a sufficient and less costly way of managing their gallstone symptoms rather than going straight on the waiting list for surgery. More research is needed to identify which patients benefit most from surgery.

Effectiveness of conservative management versus laparoscopic cholecystectomy in the prevention of recurrent symptoms and complications in adults with uncomplicated symptomatic gallstone disease (C-GALL trial): pragmatic, multicentre randomised controlled trial.

OBJECTIVE: To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease. DESIGN: Parallel group, pragmatic randomised, superiority trial. SETTING: 20 secondary care centres in the UK. PARTICIPANTS: 434 adults (>18 years) with uncomplicated symptomatic gallstone disease referred to secondary care, assessed for eligibility between August 2016 and November 2019, and randomly assigned (1:1) to receive conservative management or laparoscopic cholecystectomy. INTERVENTIONS: Conservative management or surgical removal of the gallbladder. MAIN OUTCOME MEASURES: The primary patient outcome was quality of life, measured by area under the curve, over 18 months using the short form 36 (SF-36) bodily pain domain, with higher scores (range 0-100) indicating better quality of life. Other outcomes included costs to the NHS, quality adjusted life years (QALYs), and incremental cost effectiveness ratio. RESULTS: Of 2667 patients assessed for eligibility, 434 were randomised: 217 to the conservative management group and 217 to the laparoscopic cholecystectomy group. By 18 months, 54 (25%) participants in the conservative management arm and 146 (67%) in the cholecystectomy arm had received surgery. The mean SF-36 norm based bodily pain score was 49.4 (standard deviation 11.7) in the conservative management arm and 50.4 (11.6) in the cholecystectomy arm. The SF-36 bodily pain area under the curve up to 18 months did not differ (mean difference 0.0, 95% confidence interval -1.7 to 1.7; P=1.00). Conservative management was less costly (mean difference -£1033, (-$1334; -€1205), 95% credible interval -£1413 to -£632) and QALYs did not differ (mean difference -0.019, 95% credible interval -0.06 to 0.02). CONCLUSIONS: In the short term (≤18 months), laparoscopic surgery is no more effective than conservative management for adults with uncomplicated symptomatic gallstone disease, and as such conservative management should be considered as an alternative to surgery. From an NHS perspective, conservative management may be cost effective for uncomplicated symptomatic gallstone disease. As costs, complications, and benefits will continue to be incurred in both groups beyond 18 months, future research should focus on longer term follow-up to establish effectiveness and lifetime cost effectiveness and to identify the cohort of patients who should be routinely offered surgery. TRIAL REGISTRATION: ISRCTN registry ISRCTN55215960.

Identifying Patients at Risk for Venous Thromboembolic Events After Isolated Upper Extremity Trauma: A Predictive Scale.

Previous studies have defined risk factors for development of venous thromboembolisms (VTEs) among patients with lower extremity orthopedic trauma. Limited data exist on this risk after upper extremity orthopedic trauma. A total of 269,137 incidents of upper extremity orthopedic trauma (fractures of the clavicle, scapula, humerus, elbow, or lower arm) were identified in the State Inpatient Database for 4 states included in the analysis (California, Florida, New York, and Washington) from 2006 to 2014. These patients were split into 2 cohorts, a derivation cohort (California and New York) and a validation cohort (Florida and Washington). Univariate and multivariate logistic regression analyses of risk factors for VTE within 90 days of discharge in the derivation group were used to develop the Thromboembolic Risk after Upper Extremity Trauma (TRUE-T) scale. Linear regression was used to determine fit of the TRUE-T scale to the 2 cohorts. We found that 2.61% of patients in the derivation cohort and 2.72% of patients in the validation cohort had a VTE within 90 days of discharge. Risk factors associated with increased rates of VTE were age older than 40 years, Medicare payer, anemia, chronic lung disease, coagulopathy, heart failure, malignancy, obesity, renal failure, head injury, chest injury, abdominal injury, rib fracture, humerus fracture, elbow fracture, and closed reduction. Application of the TRUE-T scale to the validation cohort showed an R2 value of 0.88. The patient factors, concomitant injuries, and fracture treatment modalities included in the TRUE-T scale can be used to identify patients at increased risk for VTE after upper extremity orthopedic trauma. [Orthopedics. 2022;45(6):345-352.].

Protocol for a randomised controlled trial comparing laparoscopic cholecystectomy with observation/conservative management for preventing recurrent symptoms and complications in adults with uncomplicated symptomatic gallstones (C-Gall trial).

BACKGROUND: Gallstone disease (cholelithiasis) is common. In most people it is asymptomatic and does not require treatment, but in about 20% it can become symptomatic, causing pain and other complications requiring medical attention and/or surgery. A proportion of symptomatic people with uncomplicated gallstone disease do not experience further episodes of pain and, therefore, could be treated conservatively. Moreover, surgery carries risks of perioperative and postoperative complications. METHODS AND ANALYSIS: C-Gall is a pragmatic, multicentre, randomised controlled trial and economic evaluation to assess whether cholecystectomy is cost-effective compared with observation/ conservative management (here after referred to as medical management) at 18 months post-randomisation (with internal pilot). PRIMARY OUTCOME MEASURE: Patient-reported quality of life (QoL) (36-Item Short Form Survey (SF-36) bodily pain domain) up to 18 months after randomisation.The primary economic outcome is incremental cost per quality-adjusted life year gained at 18 months. SECONDARY OUTCOME MEASURES: Secondary outcome measures include condition-specific QoL, SF-36 domains, complications, further treatment, persistent symptoms, healthcare resource use, and costs assessed at 18 and 24 months after randomisation. The bodily pain domain of the SF-36 will also be assessed at 24 months after randomisation.A sample size of 430 participants was calculated. Computer-generated 1:1 randomisation was used.The C-Gall Study is currently in follow-up in 20 UK research centres. The first patient was randomised on 1 August 2016, with follow-up to be completed by 30 November 2021. STATISTICAL ANALYSIS: Statistical analysis of the primary outcome will be intention-to-treat and a per-protocol analysis. The primary outcome, area under the curve (AUC) for the SF-36 bodily pain up to 18 months, will be generated using the Trapezium rule and analysed using linear regression with adjustment for the minimisation variables (recruitment site, sex and age). For the secondary outcome, SF-36 bodily pain, AUC up to 24 months will be analysed in a similar way. Other secondary outcomes will be analysed using generalised linear models with adjustment for minimisation and baseline variables, as appropriate. Statistical significance will be at the two-sided 5% level with corresponding CIs. ETHICS AND DISSEMINATION: The North of Scotland Research Ethics Committee approved this study (16/NS/0053). The dissemination plans include Health Technology Assessment monograph, international scientific meetings and publications in high-impact, open-access journals. TRIAL REGISTRATION NUMBER: ISRCTN55215960; pre-results.

A simplified preoperative risk assessment tool as a predictor of complications in the surgical management of forearm fractures.

PURPOSE: Frailty is a well-known predictor of adverse postoperative outcomes and is often considered in the preoperative planning stage of surgery. In recent years, the modified frailty index (mFI), a novel metric used to quantify frailty, has become increasingly used in the orthopedic literature as a risk assessment tool. In this study, we analyze the utility of the mFI in predicting unplanned repeat operations and morbidity in the surgical treatment forearm fractures. METHODS: We used the American College of Surgeons National Surgical Quality Improvement Program 2006-2014 dataset to identify patients undergoing open fixation of forearm fractures. The mFI was calculated based on 5 possible comorbid conditions. Demographic and predictor variables were analyzed for associations with each outcome. In order to assess frailty in both the general and elderly population, two analyses were completed: one for the entire population and one for a population of age 65 or older. The primary outcome of interest was unplanned repeat operation. Secondary outcomes included discharge destination and major post-operative complications. Chi square and logistic regression analyses were used to identify associations. RESULTS: A total of 4641 patients were included in our final analysis. There was a higher prevalence of females and patients between the ages of 61 and 80 compared to other age groups. An mFI score ≥2 was a positively associated with unplanned repeat operation in the general population. An mFI score ≥2 was also positively associated with a discharge destination other than home and major post-operative complications. In the elderly population, mFI ≥2 was similarly associated with a discharge destination other than the patient's home. CONCLUSIONS: Patients undergoing open treatment of forearm fractures were at an increased likelihood of having an unplanned repeat operation and having major complications as frailty score increased, demonstrating that the mFI may be clinically applicable risk assessment tool for these patients.

Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation.

BACKGROUND: Only a small proportion of preclinical research (research performed in animal models prior to clinical trials in humans) translates into clinical benefit in humans. Possible reasons for the lack of translation of the results observed in preclinical research into human clinical benefit include the design, conduct, and reporting of preclinical studies. There is currently no formal domain-based assessment of the clinical relevance of preclinical research. To address this issue, we have developed a tool for the assessment of the clinical relevance of preclinical studies, with the intention of assessing the likelihood that therapeutic preclinical findings can be translated into improvement in the management of human diseases. METHODS: We searched the EQUATOR network for guidelines that describe the design, conduct, and reporting of preclinical research. We searched the references of these guidelines to identify further relevant publications and developed a set of domains and signalling questions. We then conducted a modified Delphi-consensus to refine and develop the tool. The Delphi panel members included specialists in evidence-based (preclinical) medicine specialists, methodologists, preclinical animal researchers, a veterinarian, and clinical researchers. A total of 20 Delphi-panel members completed the first round and 17 members from five countries completed all three rounds. RESULTS: This tool has eight domains (construct validity, external validity, risk of bias, experimental design and data analysis plan, reproducibility and replicability of methods and results in the same model, research integrity, and research transparency) and a total of 28 signalling questions and provides a framework for researchers, journal editors, grant funders, and regulatory authorities to assess the potential clinical relevance of preclinical animal research. CONCLUSION: We have developed a tool to assess the clinical relevance of preclinical studies. This tool is currently being piloted.

Torn Between Caution and Compassion: a Dilemma for Clinicians from Black and Minority Ethnic Groups During the COVID-19 Pandemic.

The wide disparity in coronavirus disease (COVID-19)-related death rates based upon the ethnic origin is well established by now. The higher incidence of COVID-19 deaths amongst the healthcare staff belonging to black and minority ethnic (BAME) communities living in the United Kingdom has generated a great deal of concern and anxiety in clinicians. Public Health England (PHE) has outlined mitigation strategies after immense pressure from professional organisations and influential clinical leaders. Although seemingly well thought through, these measures fall short of addressing the professional, moral and emotional dilemma faced by the BAME clinicians who feel that they are being expected to choose between their duty towards their patients and the profession, and their responsibility to look after their own health.

Patient frailty as a risk assessment tool in surgical management of long bone fractures.

BACKGROUND: Frailty is an important predictor of surgical outcomes and has been quantified by several models. The modified frailty index (mFI) has recently been adapted from an 11-item index to a 5-item index and has promise to be a valuable risk assessment tool in orthopedic trauma patients. We perform a retrospective analysis of the 5-item mFI and evaluate its effectiveness in predicting outcomes in patients with long bone fractures. METHODS: The National Surgery Quality Improvement Program (NSQIP) 2006-2016 database was queried for surgical procedures in the treatment of long bone fractures by current procedural terminology (CPT) codes, excluding those performed on metacarpals and metatarsals. Cases were excluded if they were missing demographic, frailty, and variable data. The 5-item frailty index was calculated based on the sum of presence of 5 conditions: COPD/pneumonia, congestive heart failure, diabetes, hypertension, and impaired functional status. Chi square was used to determine variables significantly associated with each outcome. The significant variables were included in multivariate logistic regression along with the mFI. Significance was defined as p < 0.05. RESULTS: Of the 140,249 fixation procedures performed on long bone fractures in NSQIP, 109,423 cases remained after exclusion criteria were applied. The majority of patients were between the ages of 61 and 80 (34.0%), were female (65.6%) and Caucasian (86.3%). Multivariate analysis revealed that mFI scores ≥3 were predictive of unplanned reoperation (OR = 1.57), wound disruption (OR = 2.83), unplanned readmission (OR = 2.12), surgical site infection (OR = 1.90), major complications (OR = 3.04), and discharge destination (OR = 3.06). CONCLUSIONS: Our study analyzed the relationship of frailty and postoperative complications in patients with long bone fractures. Patients had increased likelihood of morbidity, independent of other comorbidities and demographic factors. The mFI may have a role as a simple, easy to use risk assessment tool in cases of orthopedic trauma.

Is Insurance Status Associated with the Likelihood of Operative Treatment of Clavicle Fractures?

BACKGROUND: Most closed clavicle fractures are treated nonoperatively. Research during the past decade has reported differences in the treatment of clavicle fractures based on insurance status in the US and may highlight unmet needs in a vulnerable population, particularly because new data show that surgery may lead to improved outcomes in select populations. Large-scale, national data are needed to better inform this debate. QUESTIONS/PURPOSES: (1) Does the likelihood of operative fixation of closed clavicle fractures vary among patients with different types of insurance? (2) What demographic and socioeconomic factors are associated with the likelihood of clavicle fracture surgery? (3) Has the proportion of operative fixation of clavicle fractures changed over time? METHODS: A retrospective analysis of the Nationwide Inpatient Sample 2001-2013 database was performed. This database is the largest publicly available all-payer inpatient database in the US that provides pertinent socioeconomic data on a nationwide scale. Data were queried for patients with closed clavicle fractures using International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes, and surgery was determined using ICD-9 procedural codes. A total of 252,109 patients were included in the final analysis after 158,619 patients were excluded because of missing demographic or insurance data, ambiguous fracture location, or age younger than 19 years. Of the 252,109 included patients, 21,638 (9%) underwent surgical fixation of clavicle fractures. A chi-square analysis was performed to determine variables to be included in a multivariable analysis. A binary logistic regression analysis was used to examine demographic and other important variables, with a significance level of p < 0.01. Poisson's regression and a t-test were used to analyze trends over time. Results were recorded as odds ratios (OR) and incidence rate ratios. RESULTS: After controlling for demographic and potentially relevant variables, such as the median income and fracture location, we found that patients with Medicare, Medicaid, and no insurance had a lower likelihood of undergoing operative fixation of clavicle fractures than did those with private insurance. Patients without insurance were the least likely to undergo surgery (OR, 0.63; 95% CI, 0.60-0.66; p < 0.001), followed by those with Medicare (OR, 0.73; 95% CI, 0.70-0.78; p < 0.001) and those with Medicaid (OR, 0.74; 95% CI, 0.69-0.78; p < 0.001). Women, black, and Hispanic patients were also less likely to undergo surgery than men and white patients (OR, 0.95; p = 0.003; OR = 0.67; p < 0.001; and OR = 0.82; p < 0.001, respectively) There was an increase in the overall proportion of patients undergoing surgery, from 5% in 2001 to 11% in 2013 (incidence rate ratio, 2.99; p < 0.001). CONCLUSIONS: We believe that the greater use of surgery among adult patients with clavicle fractures who have private insurance than among those with nonprivate or no insurance-as well as among men and white patients compared with women and patients of color-may be a manifestation of important health care disparities in the inpatient population. This may be owing to variable access to care or a difference in the likelihood that a surgeon will offer surgery based on a patient's insurance status. Because operative fixation of closed clavicle fractures increases in the adult population, future research should elucidate conscious and subconscious motivations of patients and surgeons to better inform the discussion of health care disparities in orthopaedics. LEVEL OF EVIDENCE: Level III, therapeutic study.

Susceptibility and resilience to cyber threat: Findings from a scenario decision program to measure secure and insecure computing behavior.

Interest in the individual differences underlying end user computer security behavior has led to the development of a multidisciplinary field of research known as behavioral information security. An important gap in knowledge and the motivation for this research is the development of ways to measure secure and insecure cyber behavior for research and eventually practice. Here we report a study designed to develop a technique for assessing secure and insecure cyber behavior for broad research use. The Susceptibility and Resilience to Cyber Threat (SRCT) is an immersive scenario decision program. The SRCT measures susceptibility to cyber threat and malicious behavior as well protective resilience actions via participant responses/decisions to emails, interactions with security dialogs, and computer actions in a real-world simulation. Data were collected from a sample of 190 adults (76.3% female), between the ages of 18-61 (mean age = 26.12). Personality, behavioral tendencies, and cognitive preferences were measured with standard previously validated protocols and self-report measures. Factor analysis suggested a 5 item secure actions scale and a 9 item insecure actions scale as viable to extract from the SRCT responses. Statistically analyzable distributions of secure and insecure cyber behaviors were obtained, and these subscales demonstrated acceptable internal consistency as hypothesized. Associations between SRCT scales and other indices of cyber behavior, as well as self-reported personality, were lower than predicted, suggesting that past research reporting links between self-reports of personality and self-reported cyber-behavior may be overestimating the links for actual cyber actions. However, our exploratory analyses suggest discrepancies between self-report and actions in the SRCT may be an interesting avenue to explore. Overall, results were consistent with theorizing and suggest the technique is viable as a construct measure in future research or as an outcome variable in experimental intervention designs.

The clinical effectiveness and cost-effectiveness of open mesh repairs in adults presenting with a clinically diagnosed primary unilateral inguinal hernia who are operated in an elective setting: systematic review and economic evaluation.

BACKGROUNDS: Current open mesh techniques for inguinal hernia repair have shown similar recurrence rates. However, chronic pain has been associated with Lichtenstein mesh repair, the most common surgical procedure for inguinal hernia in the UK. The position of the mesh is probably an important factor. The Lichtenstein method requires dissection of the inguinal wall and fixation of the mesh. In contrast, in the open preperitoneal approach the mesh is placed in the preperitoneal space and held in place with intra-abdominal pressure. Currently, there is no consensus regarding the best open approach for repair of inguinal hernia. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of open preperitoneal mesh repair compared with Lichtenstein mesh repair in adults presenting with a clinically diagnosed primary unilateral inguinal hernia. DATA SOURCES: We searched major electronic databases (e.g. MEDLINE, MEDLINE In-Process & Other Non-Indexed, EMBASE, Cochrane Controlled Trials Register) from inception to November 2014 and contacted experts in the field. REVIEW METHODS: Evidence was considered from randomised controlled trials (RCTs) that compared open preperitoneal mesh repair with Lichtenstein mesh repair for the treatment of inguinal hernia. Two reviewers independently selected studies for inclusion. One reviewer completed data extraction and assessed risk of bias for included studies, and two reviewers independently cross-checked the details extracted. Meta-analyses techniques were used to combine results from included studies. A Markov model was developed to assess the cost-effectiveness of open mesh procedures from a NHS health services perspective over a 25-year time horizon. RESULTS: Twelve RCTs involving 1568 participants were included. Participants who underwent open preperitoneal mesh repair returned to work and normal activities significantly earlier than those who underwent Lichtenstein mesh repair [mean difference -1.49 days, 95% confidence interval (CI) -2.78 to -0.20 days]. Although no significant differences were observed between the two open approaches for incidence of pain [risk ratio (RR) 0.50, 95% CI 0.20 to 1.27], numbness (RR 0.48, 95% CI 0.15 to 1.56), recurrences (Peto odds ratio 0.76, 95% CI 0.38 to 1.52) or postoperative complications, fewer events were generally reported after open preperitoneal mesh repair. The results of the economic evaluation indicate that the open preperitoneal mesh repair was £256 less costly and improved health outcomes by 0.041 quality-adjusted life-years (QALYs) compared with Lichtenstein mesh repair. The open preperitoneal procedure was the most efficient and dominant treatment strategy with a high (> 98%) probability of being cost-effectiveness for the NHS at a willingness to pay of £20,000 for a QALY. Results were robust to a range of sensitivity analyses. However, the magnitude of cost saving or QALY gain was sensitive to some model assumptions. LIMITATIONS: Overall, the included trials were of small sample size (mean 130.7 participants) and at high or unclear risk of bias. Meta-analyses results demonstrated significant statistical heterogeneity for most of the assessed outcomes. CONCLUSIONS: Open preperitoneal mesh repair appears to be a safe and efficacious alternative to Lichtenstein mesh repair. Further research is required to determine the long-term effects of these surgical procedures as well as the most effective open preperitoneal repair technique in terms of both clinical efficacy and costs. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014013510. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Systematic review of the clinical and cost effectiveness of cholecystectomy versus observation/conservative management for uncomplicated symptomatic gallstones or cholecystitis.

BACKGROUND: Gallstone disease is a common gastrointestinal disorder in industrialised countries. Although symptoms can be severe, some people can be symptom free for many years after the original attack. Surgery is the current treatment of choice, but evidence suggests that observation is also feasible and safe. We reviewed the evidence on cholecystectomy versus observation for uncomplicated symptomatic gallstones and conducted a cost-effectiveness analysis. METHODS: We searched six electronic databases (last search April 2014). We included randomised controlled trials (RCTs) or non-randomised comparative studies where adults received either cholecystectomy or observation/conservative management for the first episode of symptomatic gallstone disease (biliary pain or cholecystitis) being considered for surgery in secondary care. Meta-analysis was used to combine results. A de novo Markov model was developed to assess the cost effectiveness of the interventions. RESULTS: Two RCTs (201 participants) were included. Eighty-eight percent of people randomised to surgery and 45 % of people randomised to observation underwent cholecystectomy during the 14-year follow-up period. Participants randomised to observation were significantly more likely to experience gallstone-related complications (RR = 6.69, 95 % CI = 1.57-28.51, p = 0.01), in particular acute cholecystitis (RR = 9.55, 95 % CI = 1.25-73.27, p = 0.03), and less likely to undergo surgery (RR = 0.50, 95 % CI = 0.34-0.73, p = 0.0004) or experience surgery-related complications (RR = 0.36, 95 % CI = 0.16-0.81, p = 0.01) than those randomised to surgery. Fifty-five percent of people randomised to observation did not require surgery, and 12 % of people randomised to cholecystectomy did not undergo surgery. On average, surgery costs £1,236 more per patient than conservative management, but was more effective. CONCLUSIONS: Cholecystectomy is the preferred treatment for symptomatic gallstones. However, approximately half the observation group did not require surgery or suffer complications indicating that it may be a valid alternative to surgery. A multicentre trial is needed to establish the effects, safety and cost effectiveness of observation/conservative management relative to cholecystectomy.

Clinical effectiveness and cost-effectiveness of cholecystectomy compared with observation/conservative management for preventing recurrent symptoms and complications in adults presenting with uncomplicated symptomatic gallstones or cholecystitis: a systematic review and economic evaluation.

BACKGROUND: Approximately 10-15% of the adult population suffer from gallstone disease, cholelithiasis, with more women than men being affected. Cholecystectomy is the treatment of choice for people who present with biliary pain or acute cholecystitis and evidence of gallstones. However, some people do not experience a recurrence after an initial episode of biliary pain or cholecystitis. As most of the current research focuses on the surgical management of the disease, less attention has been dedicated to the consequences of conservative management. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of cholecystectomy compared with observation/conservative management in people presenting with uncomplicated symptomatic gallstones (biliary pain) or cholecystitis. DATA SOURCES: We searched all major electronic databases (e.g. MEDLINE, EMBASE, Science Citation Index, Bioscience Information Service, Cochrane Central Register of Controlled Trials) from 1980 to September 2012 and we contacted experts in the field. REVIEW METHODS: Evidence was considered from randomised controlled trials (RCTs) and non-randomised comparative studies that enrolled people with symptomatic gallstone disease (pain attacks only and/or acute cholecystitis). Two reviewers independently extracted data and assessed the risk of bias of included studies. Standard meta-analysis techniques were used to combine results from included studies. A de novo Markov model was developed to assess the cost-effectiveness of the interventions. RESULTS: Two Norwegian RCTs involving 201 participants were included. Eighty-eight per cent of people randomised to surgery and 45% of people randomised to observation underwent cholecystectomy during the 14-year follow-up period. Participants randomised to observation were significantly more likely to experience gallstone-related complications [risk ratio = 6.69; 95% confidence interval (CI) 1.57 to 28.51; p = 0.01], in particular acute cholecystitis (risk ratio = 9.55; 95% CI 1.25 to 73.27; p = 0.03), and less likely to undergo surgery (risk ratio = 0.50; 95% CI 0.34 to 0.73; p = 0.0004), experience surgery-related complications (risk ratio = 0.36; 95% CI 0.16 to 0.81; p = 0.01) or, more specifically, minor surgery-related complications (risk ratio = 0.11; 95% CI 0.02 to 0.56; p = 0.008) than those randomised to surgery. Fifty-five per cent of people randomised to observation did not require an operation during the 14-year follow-up period and 12% of people randomised to cholecystectomy did not undergo the scheduled operation. The results of the economic evaluation suggest that, on average, the surgery strategy costs £1236 more per patient than the conservative management strategy but was, on average, more effective. An increase in the number of people requiring surgery while treated conservatively corresponded to a reduction in the cost-effectiveness of the conservative strategy. There was uncertainty around some of the parameters used in the economic model. CONCLUSIONS: The results of this assessment indicate that cholecystectomy is still the treatment of choice for many symptomatic people. However, approximately half of the people in the observation group did not require surgery or suffer complications in the long term indicating that a conservative therapeutic approach may represent a valid alternative to surgery in this group of people. Owing to the dearth of current evidence in the UK setting a large, well-designed, multicentre trial is needed. STUDY REGISTRATION: The study was registered as PROSPERO CRD42012002817. FUNDING: The National Institute for Health Research Health Technology Assessment programme.