Controlling unmeasured confounders in non-randomized controlled studies is challenging. Negative control theory is based on the theoretical concept that the test result of negative controls must be negative. Setting appropriate negative control incorporates the specificity of association into population studies for the identification and control of unmeasured confounders. This paper explains the principles to control unmeasured confounders using negative control theory from a statistical perspective. A detailed introduction of derived methods based on negative control theory is also introduced, including adjusted standardized mortality ratio method, calibrating P-value method, generalized difference-in-difference model and double negative control method. The reasonable application of those derived methods is also comprehensively summarized based on representative case studies. Negative control is an important statistical design to identify, revise and control unmeasured confounders and a valuable method for comparative effectiveness research based on real-world data.
Humans ; Confounding Factors, Epidemiologic ; Research Design ; Comparative Effectiveness Research ; Bias

No abstract available.
Comparative Effectiveness Research

PURPOSE: Extrafine-particle inhaled corticosteroids (ICS) have greater small airway deposition than standard fine-particle ICS. We sought to compare asthma-related outcomes after patients initiated extrafine-particle ciclesonide or fine-particle ICS (fluticasone propionate or non-extrafine beclomethasone). METHODS: This historical, matched cohort study included patients aged 12-60 years prescribed their first ICS as ciclesonide or fine-particle ICS. The 2 cohorts were matched 1:1 for key demographic and clinical characteristics over the baseline year. Co-primary endpoints were 1-year severe exacerbation rates, risk-domain asthma control, and overall asthma control; secondary endpoints included therapy change. RESULTS: Each cohort included 1,244 patients (median age 45 years; 65% women). Patients in the ciclesonide cohort were comparable to those in the fine-particle ICS cohort apart from higher baseline prevalence of hospitalization, gastroesophageal reflux disease, and rhinitis. Median (interquartile range) prescribed doses of ciclesonide and fine-particle ICS were 160 (160-160) µg/day and 500 (250-500) µg/day, respectively (P<0.001). During the outcome year, patients prescribed ciclesonide experienced lower severe exacerbation rates (adjusted rate ratio [95% CI], 0.69 [0.53-0.89]), and higher odds of risk-domain asthma control (adjusted odds ratio [95% CI], 1.62 [1.27-2.06]) and of overall asthma control (2.08 [1.68-2.57]) than those prescribed fine-particle ICS. The odds of therapy change were 0.70 (0.59-0.83) with ciclesonide. CONCLUSIONS: In this matched cohort analysis, we observed that initiation of ICS with ciclesonide was associated with better 1-year asthma outcomes and fewer changes to therapy, despite data suggesting more difficult-to-control asthma. The median prescribed dose of ciclesonide was one-third that of fine-particle ICS.
Adrenal Cortex Hormones* ; Anti-Asthmatic Agents ; Asthma ; Cohort Studies ; Comparative Effectiveness Research ; Diethylpropion ; Disease Progression ; Gastroesophageal Reflux ; Hospitalization ; Humans ; Odds Ratio ; Prevalence ; Rhinitis

To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC).The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups.There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra- or extrahepatic HCC on MRI between cTACE group and DEB-TACE group.There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.
Carcinoma, Hepatocellular ; diagnostic imaging ; therapy ; Chemoembolization, Therapeutic ; adverse effects ; instrumentation ; methods ; Comparative Effectiveness Research ; Drug Delivery Systems ; instrumentation ; methods ; Epirubicin ; administration & dosage ; therapeutic use ; Humans ; Liver Neoplasms ; Magnetic Resonance Imaging ; Microspheres ; Neoplasm Recurrence, Local ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo systematically assess the safety and efficacy of hand-assisted laparoscopic distal gastrectomy (HALG) versus open distal gastrectomy (ODG) for gastric cancer.

METHODSChinese or English literature regarding comparison of HALG and ODG were collected by searching in databases (such as PubMed, Cochrane Library, CNKI, Wanfang database) between January 1996 and September 2016. The data of operative time, incision length, blood loss, number of harvested lymph nodes, time to flatus, hospital stay, postoperative complication morbidity and long-term outcomes were compared between the two procedures. Then funnel plot was used to evaluate publication bias and sensitivity analysis was used to evaluate the stability of the results. All these data analyses were performed using the Meta for or Meta package of R version 3.3.1.

RESULTSA total of 7 studies with 835 patients (323 cases in HALG group and 512 cases in ODG group) were included. Compared with ODG, HALG had a longer operative time (WMD=28.93 minutes, 95%CI=9.59 to 48.28, Z=2.93, P=0.000), a shorter incision length (WMD=-10.31 cm, 95%CI=-14.01 to -6.62, Z=-5.47, P=0.000), less blood loss (WMD=-140.08 ml, 95%CI=-215.07 to -65.09, Z=-3.66, P=0.000), faster gastrointestinal recovery (WMD=-1.23 days, 95%CI=-1.89 to -0.56, Z=-3.62, P=0.000), shorter postoperative hospital stay (WMD=-3.24 days, 95%CI=-5.47 to -1.02, Z=-2.85, P=0.000). In subgroup analysis, 3 studies published before 2013 vs. 4 studies published afterwards, the number of harvested lymph nodes (WMD=-0.78, 95%CI=-2.05 to 0.50, Z=-1.19, P=0.235) and postoperative complication morbidity (RR=1.02, 95%CI=0.43 to 2.44, Z=0.05, P=0.961) did not differ significantly between two groups. Compared with ODG, the RR(95%CI) of ileus of HALG was 0.43 (0.07 to 2.82), but the difference was not statistically significant (P=0.383). One study reported the 5-year overall survival rates of HALG and ODG were 81.0% vs 67.5%, and the tumor recurrence rates were 7.1% vs 22%, respectively, but the differences were not statistically significant(all P>0.05). Sensitivity analysis showed that the above results were stable. The funnel plots of the lymph nodes and postoperative complication morbidity did not present significant publication bias.

CONCLUSIONSHALG has the advantages of minimal invasiveness such as shorter incision length and quicker recovery. Furthermore, the short-term efficacy of HALG is similar to conventional open surgery. However, the long-term efficacy is lack of support from multicenter long-term follow-up results.

Blood Loss, Surgical ; statistics & numerical data ; Comparative Effectiveness Research ; Gastrectomy ; methods ; Hand-Assisted Laparoscopy ; adverse effects ; Humans ; Length of Stay ; statistics & numerical data ; Lymph Node Excision ; statistics & numerical data ; Neoplasm Recurrence, Local ; epidemiology ; Operative Time ; Postoperative Complications ; epidemiology ; Postoperative Period ; Recovery of Function ; Stomach Neoplasms ; mortality ; surgery ; Survival Rate ; Time ; Treatment Outcome

OBJECTIVETo compared the clinical efficacy of laparoscopic repair (LR) versus open repair (OR) for perforated peptic ulcers.

METHODSFrom January 2010 to June 2014, in Shanghai Tongji Hospital, 119 patients who were diagnosed as perforated peptic ulcers and planned to receive operation were prospectively enrolled. Patients were randomly divided into LR (58 patients) and OR(61 patients) group by computer. Intra-operative and postoperative parameters were compared between two groups. This study was registered as a randomized controlled trial by the China Clinical Trials Registry (registration No.ChiCTR-TRC-11001607).

RESULTSThere was no significant difference in baseline data between two groups (all P>0.05). No significant differences of operation time, morbidity of postoperative complication, mortality, reoperation probability, decompression time, fluid diet recovery time and hospitalization cost were found between two groups (all P>0.05). As compared to OR group, LR group required less postoperative fentanyl [(0.74±0.33) mg vs. (1.04±0.39) mg, t=-4.519, P=0.000] and had shorter hospital stay [median 7(5 to 9) days vs. 8(7 to 10) days, U=-2.090, P=0.001]. In LR group, 3 patients(5.2%) had leakage in perforation site after surgery. One case received laparotomy on the second day after surgery for diffuse peritonitis. The other two received conservative treatment (total parenteral nutrition and enteral nutrition). There was no recurrence of perforation in OR group. One patient of each group died of multiple organ dysfunction syndrome (MODS) 22 days after surgery.

CONCLUSIONLR may be preferable for treating perforated peptic ulcers than OR, however preventive measures during LR should be taken to avoid postopertive leak in perforation site.

China ; Comparative Effectiveness Research ; Digestive System Surgical Procedures ; adverse effects ; methods ; Enteral Nutrition ; Female ; Fentanyl ; Humans ; Laparoscopy ; adverse effects ; rehabilitation ; Laparotomy ; Length of Stay ; statistics & numerical data ; Male ; Multiple Organ Failure ; epidemiology ; Operative Time ; Pain, Postoperative ; drug therapy ; epidemiology ; Parenteral Nutrition, Total ; Peptic Ulcer Perforation ; rehabilitation ; surgery ; Peritonitis ; therapy ; Postoperative Complications ; epidemiology ; therapy ; Postoperative Period ; Prospective Studies ; Recurrence ; Reoperation ; Treatment Outcome

OBJECTIVETo compare the postoperative analgesia efficacy, rehabilitation parameters and complication between multimodal analgesia and traditional analgesia after radical gastrectomy for gastric cancer patients.

METHODSPatients with gastric cancer who underwent surgery in our hospital from October 2016 to December 2016 were enrolled in this prospective study. According to the non-randomized method, patients were assigned to multimodal analgesia group(n=32) and traditional analgesia group(n=33) in gastric cancer treatment team A and B in Department of Gastrointestinal Surgery, West China Hospital, Sichuan University. The treatment measures of group A were as follows: (1) The ratio of 1/1 diluted ropivacaine (100 mg, 10 ml) was infiltrated around the incision before abdomen closure, with incision sutured layer by layer. (2) Parecoxib sodium (40 mg) was injected intravenously every 12 hours after operation for 5 days. (3) Oxycodone-acetaminophen tablet was given orally on the first day or the second day after operation, 50 mg twice a day. (4) Patient-controlled analgesia was not used after operation. Patients in group B received direct suture of incision and patient-controlled analgesia. The pain score, postoperative rehabilitation and 30-day postoperative complications were collected and analyzed.

RESULTSMultimodal analgesia group had lower pain scores at 1 d (4.8±0.9), 2 d (4.3±1.0), 3 d (2.9±0.8), 4 d (2.4±0.7) and 5 d (1.7±0.7) after surgery, as compared to traditional analgesia group (5.9±0.9, P=0.000), (5.1±0.7, P=0.001), (3.9±0.8, P=0.000), (3.0±0.6, P=0.000), (2.6±0.7, P=0.000), with significant difference. Postoperative hospital stay [(8.2±1.6) days vs. (10.6±2.2) days, P=0.000], time to ambulation [(47.5±13.8) days vs. (66.2±16.8) days, P=0.000], time to first flatus [(76.4±25.2) days vs. (120.0±29.9) days, P=0.000], time to first defecate [(117.3±42.2) days vs. (159.7±30.7) days, P=0.000] and time to first fluid diet [(83.8±21.6) days vs. (141.9±33.9) days, P=0.000] in the multimodal analgesia group were significantly shorter than those in the traditional analgesia group. There was no significant difference between the two groups with respect to 30-day postoperative complication rate(9.4% vs. 9.1%, P=1.000).

CONCLUSIONSMultimodal analgesia can significantly reduce the postoperative pain and is beneficial to rehabilitation, meanwhile it does not increase the risk of postoperative complications. Multimodal analgesia is safe and effective for gastric cancer patients undergoing radical gastrectomy.

Acetaminophen ; administration & dosage ; therapeutic use ; Amides ; administration & dosage ; therapeutic use ; Analgesia, Patient-Controlled ; China ; Comparative Effectiveness Research ; Defecation ; Drug Combinations ; Eating ; Flatulence ; Gastrectomy ; rehabilitation ; Humans ; Isoxazoles ; administration & dosage ; therapeutic use ; Length of Stay ; statistics & numerical data ; Oxycodone ; administration & dosage ; therapeutic use ; Pain Management ; methods ; Pain, Postoperative ; drug therapy ; Postoperative Complications ; Prospective Studies ; Recovery of Function ; drug effects ; Stomach Neoplasms ; surgery ; Surgical Wound ; rehabilitation ; therapy ; Suture Techniques ; Treatment Outcome ; Walking

OBJECTIVETo compare clinically relevant postoperative complications after open, laparoscopic, and robotic gastrectomy for gastric cancer.

METHODSClinical data of patients with gastric cancer who underwent gastrectomy between January 1, 2014 and October 1, 2016 at Chinese People's Liberation Army General Hospital were analyzed retrospectively. All the patients were diagnosed by upper endoscopy and confirmed by biopsy without distant metastasis. They were confirmed with R0 resection by postoperative pathology. Patients with incomplete data were excluded. The complications among open group, laparoscopic group and robotic group were compared. The continuous variables were analyzed by one-way ANOVA, and categorical variables were analyzed by χtest or Fisher exact test.

RESULTSA total of 1 791 patients (1 320 males and 471 females) were included in the study, aged from 17 to 98 (59.0±11.6) years, comprising 922 open, 673 laparoscopic and 196 robotic gastrectomies. There were no significant differences among three groups in baseline data (gender, age, BMI, comorbidity, radiochemotherapy) and some of operative or postoperative data (blood transfusion, number of lymph node dissection, combined organ resection, resection site, N stage, postoperative hospital stay). The blood loss in laparoscopic and robotic groups was significantly lower than that in open group[(185.7±139.6) ml and (194.0±187.6) ml vs. (348.2±408.5) ml, F=59.924, P=0.000]. The postoperative complication occurred in 197 of 1 791(11.0%) patients. The Clavien-Dindo II(, III(a, III(b, IIII(a, and IIIII( complications were 5.5%, 4.0%, 1.2%, 0.1%, and 0.2% respectively. The anastomotic leakage (2.4%), intestinal obstruction(1.3%) and pulmonary infection(1.2%) were the three most common complications, followed by wound infection(0.8%), cardiovascular disease(0.7%), anastomotic bleeding (0.7%), delayed gastric emptying (0.6%), duodenal stump fistula(0.5%), intraperitoneal hemorrhage (0.5%), pancreatic fistula (0.3%), intra-abdominal infection(0.2%), chylous leakage (0.1%) and other complications(1.7%). There were no significant differences among three groups as the complication rates of open, laparoscopic and robotic gastrectomy were 10.6%(98/922), 10.8%(73/673) and 13.3%(26/196) respectively (χ=1.173, P=0.566). But anastomotic leakage occurred more common after laparoscopic and robotic gastrectomy compared to open gastrectomy [3.1%(21/673) and 5.1%(10/196) vs. 1.3%(12/922), χ=12.345, P=0.002]. The rate of cardiocerebral vascular diseases was higher in open group[1.3%(12/922) vs. 0.1%(1/673) and 0, χ=8.786, P=0.012]. And the rate of anastomotic bleeding was higher in robotic group [2.0%(4/196) vs. open 0.4%(4/922) and laparoscopic 0.6%(4/673), χ=6.365, P=0.041]. In view of Clavien-Dindo classification, III(a complications occurred more common in laparoscopic group [5.5%(37/673) vs. open 3.3%(30/922) and robotic 2.6%(5/196), χ=6.308, P=0.043] and III(b complications occurred more common in robotic group [3.1%(6/196) vs. open 1.1%(10/922) and laparoscopic 0.7%(5/673), χ=7.167, P=0.028].

CONCLUSIONSMorbidities of postoperative complications are comparable among open, laparoscopic and robotic gastrectomy for gastric cancer. However, in consideration of the high difficulty of anastomosis, the minimally invasive surgery should be performed by more experienced surgeons.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anastomotic Leak ; epidemiology ; etiology ; Blood Loss, Surgical ; statistics & numerical data ; Cerebrovascular Disorders ; epidemiology ; etiology ; Chylous Ascites ; epidemiology ; etiology ; Comorbidity ; Comparative Effectiveness Research ; Duodenal Diseases ; epidemiology ; etiology ; Female ; Gastrectomy ; adverse effects ; methods ; Gastrointestinal Hemorrhage ; epidemiology ; etiology ; Gastroparesis ; epidemiology ; etiology ; Gastroscopy ; Hemoperitoneum ; epidemiology ; etiology ; Humans ; Intestinal Fistula ; epidemiology ; etiology ; Intraabdominal Infections ; epidemiology ; etiology ; Laparoscopy ; adverse effects ; Length of Stay ; Lymph Node Excision ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; etiology ; Postoperative Hemorrhage ; epidemiology ; etiology ; Postoperative Period ; Respiratory Tract Infections ; epidemiology ; etiology ; Retrospective Studies ; Risk Assessment ; Robotic Surgical Procedures ; adverse effects ; Stomach Neoplasms ; surgery ; Surgical Wound Infection ; epidemiology ; etiology

OBJECTIVETo evaluate the feasibility and safety of the delta-shaped anastomosis in laparoscopic distal gastrectomy and digestive tract reconstruction.

METHODSClinical data of 34 gastric cancer patients undergoing laparoscopic distal gastrectomy with the delta-shaped anastomosis for digestive tract reconstruction (delta-shaped group) and 83 gastric cancer patients undergoing laparoscopic distal gastrectomy with Billroth I( for digestive tract reconstruction (Billroth group) by same surgeon team from July 2013 to July 2015 at the Department of Digestive Surgery, Affiliated Tumor Hospital of Shanxi Medical University were retrospectively analyzed. Data of two groups were compared.

RESULTAge, gender, tumor stage were not significantly different between the two groups(all P>0.05). Operation time of the first 15 cases in delta-shaped group was longer than that in Billroth group [(254.7±35.4) min vs. (177.8±33.0) min, t=11.190, P=0.000], while after above 15 cases, the operation time of delta-shaped group was significantly shorter than that of Billroth group [(142.1±14.6) min vs. (177.8±33.0) min, t=-4.109, P=0.001]. Delta-shaped group had less blood loss during operation [(87.1±36.7) ml vs. (194.0±55.1) ml, t=-10.268, P=0.000], and shorter length of incision [(4.1±0.4) cm vs. (6.1±1.0) cm, t=-10.331, P=0.000] than Billroth group. Compared with Billroth group, delta-shaped group presented faster postoperative bowel function return [(2.8±0.6) d vs. (3.3±0.5) d, t=-3.755, P=0.000], earlier liquid food intake [(7.4±1.5) d vs. (8.1±1.7) d, t=-4.135, P=0.000], earlier ambulation [(4.0±1.6) d vs. (6.8±1.4) d, t=-7.197, P=0.000] and shorter postoperative hospital stay [(12.6±1.9) d vs.(13.6±2.0) d, t=-20.149, P=0.000]. Morbidity of postoperative complication was 5.9%(2/34) in delta-shaped group, including anastomotic fistula in 1 case and incision infection in 1 case, and 6.0%(5/83) in Billroth group, including anastomotic fistula, incision infection, anastomotic stricture and dumping syndrome, without significant difference(P>0.05). Difference value of total protein and albumin between pre-operation and post-operation, and average decreased value of total protein, albumin, body weight between pre-operation and postoperative 6-month were not significantly different between two groups(all P>0.05). As for patients with BMI > 25 kg/m, compared to Billroth group, delta-shaped group presented less blood loss during operation [(94.1±36.7) ml vs. (203.0±55.1) ml, t=-10.268, P=0.000], lower injective dosage of postoperative analgesics [(1.9±1.1) ampule vs.(3.3±2.0) ampule, t=-2.188, P=0.032], faster intestinal recovery [(2.9±0.7) d vs. (3.2±0.9) d, t=-3.755, P=0.009], shorter hospital stay [(10.5±1.2) d vs. (11.7±1.5) d, t=-2.026, P=0.004], and lower morbidity of postoperative complication [7.1%(1/14) vs. 13.6%(3/22), χ=4.066, P=0.031].

CONCLUSIONIn laparoscopic distal gastrectomy and digestive tract reconstruction, the delta-shaped anastomosis is safe and feasible, especially suitable for obese patients.

Anastomosis, Surgical ; adverse effects ; methods ; Blood Loss, Surgical ; statistics & numerical data ; Comparative Effectiveness Research ; Constriction, Pathologic ; epidemiology ; etiology ; Defecation ; Digestive System Fistula ; epidemiology ; etiology ; Drinking ; Dumping Syndrome ; epidemiology ; etiology ; Female ; Gastrectomy ; adverse effects ; methods ; Gastroenterostomy ; adverse effects ; methods ; Humans ; Laparoscopy ; adverse effects ; methods ; Length of Stay ; Male ; Operative Time ; Postoperative Complications ; epidemiology ; Postoperative Period ; Recovery of Function ; Retrospective Studies ; Stomach Neoplasms ; surgery ; Surgical Wound ; Surgical Wound Infection ; epidemiology ; Treatment Outcome

OBJECTIVETo investigate the safety, feasibility and long-term outcomes of laparoscopic complete mesocolic excision for the transverse colon cancer.

METHODSClinical data of 61 patients who underwent laparoscopic complete mesocolic excision for transverse colon cancer (transverse group) in our department from January 2011 to January 2014 were retrospectively analyzed, which were compared with those of 155 patients undergoing laparoscopic complete mesocolic excision for ascending colon cancer (ascending group) and 230 patients undergoing laparoscopic complete mesocolic excision for sigmoid colon cancer (sigmoid group). Differences in operative details, postoperative recovery, postoperative complications and long-term survival among 3 groups were evaluated.

RESULTSNo significant differences in the baseline information were found among 3 groups(all P>0.05). The average operative time was significantly longer in transverse group as compared to ascending group and sigmoid group [(192.1±58.7) min vs. (172.2±54.7) min and (169.1±53.6) min]( P<0.05), while the blood loss [(89.7±63.6) ml, (86.3±66.3) ml, (82.6±61.5) ml], conversion rate [3.3%(2/61), 2.6%(4/155), 2.2%(5/230)], number of harvested lymph node (13.0±4.7, 14.4±6.5, 13.4±5.6), time to flatus [(2.7±1.1) d, (2.6±1.1) d, (2.5±1.0) d], time to liquid diet [(3.0±1.7) d, (2.8±1.5) d, (2.7±1.4) d], incidence of postoperative complication(6.6%, 9.0%, 11.7%), and hospital stay [(11.6±5.8) d, (10.7±5.8) d, (10.6±5.7) d] among 3 groups were not significantly different (all P>0.05). A total of 436 patients received postoperative follow-up of median 36 (5 to 67) months. The overall 5-year survival rate was 73.1%, 73.7% and 74.8%, and the 5-year disease-free survival rate was 71.5%, 71.1% and 72.7% in transverse, ascending and sigmoid colon cancer groups respectively, whose differences were not significant among 3 groups (all P>0.05).

CONCLUSIONLaparoscopic complete mesocolic excision for transverse colon cancer is safe and feasible with slightly longer operation time, and has quite good long-term oncologic efficacy.

Colectomy ; methods ; Colon, Ascending ; surgery ; Colon, Sigmoid ; surgery ; Colon, Transverse ; surgery ; Colonic Neoplasms ; surgery ; Comparative Effectiveness Research ; Disease-Free Survival ; Humans ; Laparoscopy ; methods ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Mesocolon ; surgery ; Operative Time ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Survival Rate ; Treatment Outcome