The Effects of COVID-19 on General Surgery Residency Programs in the United States.

Introduction: The COVID-19 pandemic impacted multiple aspects of surgical education. This survey delineates steps taken by general surgery residency programs to meet changing patient-care needs while continuing to provide adequate education. Methods: A survey was administered to program directors and coordinators of all United States general surgery residency programs to assess the early effects of the pandemic on residents from March 1 through May 31, 2020. Results: Of 303 programs contacted, 132 (43.6%) completed the survey. Residents were asked to work in areas outside of their specialty at 27.3% of programs. Residency curriculum was changed in 35.6% of programs, and 76.5% of programs changed their academic conferences. Resident schedules were altered at a majority of programs to limit resident-patient exposure, increase ICU coverage, or improve resident utilization. Surgical caseloads decreased at 93.8% of programs; 31.8% of those programs reported concerns regarding residents' achieving the minimum case numbers required to graduate. Conclusions: These results provided insight into the restructuring of general surgery residency programs during a pandemic and may be used to establish future pandemic response plans.

Infralingular Versus Supralingular Medial Osteotomy in Sagittal Split Osteotomy of the Mandible: A Randomized Control Study.

PURPOSE: A recently proposed modification of the sagittal split osteotomy (SSO) of the mandible places the horizontal medial cut 'low and short' of the lingula. The purpose of the study was to answer the following clinical question: Among patients undergoing mandibular setback procedures (≤ 8 mm) via SSO, does the placement of the medial horizontal osteotomy below the lingula (infralingular), when compared to placement above the lingula (supralingular), results in different neurosensory, bite force, and range of motion outcomes? MATERIALS AND METHODS: This was a single-center, double-blind, parallel-group study among patients undergoing mandibular setback by SSO (≤ 8 mm), between January 2021 and September 2022. Patients were randomly allocated in a ratio of 1:1 to the supralingular (control) and the infralingular (study) group. Primary outcome variables included neurosensory disturbance of the inferior alveolar nerve based on clinical neurosensory testing and severity graded using Zuniga and Essick's protocol, bite force, and maximum mouth opening evaluated postoperatively during the first week (T1), first month (T2), and third month (T3) of follow-up. Secondary outcome measures included the incidence of a bad split and distal segment interferences intraoperatively. Association between the variables was assessed using Pearson chi-squared test or Fisher's exact test based on the expected observations. A P value of ≤.05 was considered statistically significant. RESULTS: A total of 29 patients (58 osteotomies) were included in the study. Group 1 consisted of 15 patients (9 females and 6 males) with a mean age of 26.4 years. Group 2 consisted of 14 patients (8 females and 6 males) with a mean age of 25.9 years. Patients with severe neurosensory disturbance of the inferior alveolar nerve were more common in group 2 (n = 15, 53.6%) than group 1 (n = 4, 13.3%) at T1 (P value = .0001) and insignificant between the two groups at T2 (P value = .63) and T3 (P value = .99). Comparison of maximum mouth opening between the two groups at T1 (P value = .535), T2 (P value = .934), and T3 (P value = .703) and bite force at T1 (P = .324), T2 (P = .113), and T3 (P = .811) was not significant. CONCLUSION: Both SSO techniques have similar clinical outcomes among patients having mandibular setbacks (≤ 8 mm) for the variables studied.

Tibial Plateau Leveling Following Tibial Tuberosity Advancement: A Case Series.

Persistent stifle instability is a recognized complication following tibial tuberosity advancement techniques (TTAT). The aim of this study is to report the feasibility and outcome of tibial plateau leveling techniques (TPLT) to treat dogs with persistent lameness, suspected to be secondary to persistent stifle instability, following (TTAT). Medical records of dogs presented for persistent lameness after TTAT were reviewed. Preoperative data included orthopedic examination, lameness score and radiographs. Inclusion criteria included performance of a surgery to address persistent lameness and suspected instability. Short-term follow up data included orthopedic examination and radiographs of the stifle. Long-term follow up was based on postoperative Liverpool Osteoarthritis in Dogs (LOAD) questionnaire. Seven dogs were included in the study. Mean subjective preoperative lameness score was 3 ± 1.53. Mean preoperative patellar ligament angle relative to the tibial plateau (PLATP) was 94° and mean tibial plateau angle (TPA) was 28°. Six dogs had tibial plateau leveling osteotomy and one had modified cranial closing wedge ostectomy. Mean postoperative PLATP was 79° and mean TPA was 5°. Mean subjective lameness score at follow up was 0.57 ± 0.49. Minor complications were present in 2 dogs and major complication in 1 dog. Mean LOAD questionnaire score was 6.6/52. TPLT can be performed after TTAT and may improve clinical function and stability in these cases in which persistent instability is suspected.

Long-term tolerability and efficacy of golimumab in active non-radiographic axial spondyloarthritis: results from open-label extension.

OBJECTIVES: We report the open-label extension (OLE) of the GO-AHEAD study evaluating the long-term efficacy and safety of golimumab (GLM) in patients with non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: Patients [both GLM- and placebo (PBO)-treated in the double-blind phase] received GLM 50 mg every 4 weeks during the OLE (36-week treatment; additional 8-week safety follow-up; GLM/GLM and PBO/GLM groups). All patients who entered and received ≥1 dose of study treatment in the OLE were included in the efficacy and safety analyses. The primary efficacy evaluations were the proportions of patients achieving 20% and 40% improvement in the ASAS criteria (ASAS20 and ASAS40, respectively). Responders' analyses were calculated using a non-responder imputation approach. RESULTS: Of 198 patients randomised, 189/198 (95.5%) entered the OLE; 174/198 patients (87.9%) completed all visits. Although the proportion of responders increased from week 16 to week 52 in the OLE in both GLM/GLM and PBO/GLM groups, the GLM/GLM group had a higher proportion of responders than the PBO/GLM group throughout the OLE from week 16 to week 52 (ASAS20: 71.1% to 83.9% vs 40.0% to 75.0%, respectively; ASAS40: 56.7% to 76.3% vs 23.0% to 59.4%, respectively; ASAS partial remission: 33.0% to 53.8% and 18.0% to 45.8%). In the OLE, the overall incidence of AEs was lower in the GLM/GLM vs PBO/GLM groups (41.9% and 54.2%). CONCLUSIONS: Sustained improvement in clinical efficacy was observed at 52 weeks in patients with nr-axSpA following GLM treatment. GLM was well tolerated and provided substantial long-term benefits to patients with nr-axSpA. TRIAL REGISTRATION: NCT01453725; United States National Library of Medicine clinical trials database; www.clinicaltrials.gov.

Late-term effects of hypofractionated chest wall and regional nodal radiotherapy with two-dimensional technique in patients with breast cancer.

PURPOSE: Hypofractionated radiotherapy (RT) is becoming a new standard in postoperative treatment of patients with early stage breast cancer after breast conservation surgery. However, data on hypofractionation in patients with advanced stage disease who undergo mastectomy followed by local and regional nodal irradiation (RNI) is lacking. In this retrospective study, we report late-term effects of 3 weeks post-mastectomy hypofractionated local and RNI with two-dimensional (2D) technique in patients with stage II and III breast cancer. METHODS: Between January 1990 and December 2007, 1,770 women with breast cancer who were given radical treatment with mastectomy, systemic therapy and RT at least 10 years ago were included. RT dose was 35 Gy/15 fractions/3 weeks to chest wall by two tangential fields and 40 Gy in same fractions to supraclavicular fossa (SCF) and internal mammary nodes (IMNs). SCF and IMNs dose was prescribed at dmax and 3 cm depth, respectively. Chemotherapy and hormonal therapy was given in 64% and 74% patients, respectively. Late-term toxicities were assessed with the Radiation Therapy Oncology Group (RTOG) scores and LENT-SOMA scales (the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic scales). RESULTS: Mean age was 48 years (range, 19 to 75 years). Median follow-up was 12 years (range, 10 to 27 years). Moderate/marked arm/shoulder pain was reported by 254 (14.3%) patients. Moderate/marked shoulder stiffness was reported by 219 (12.3%) patients. Moderate/marked arm edema was seen in 131 (7.4%) patients. Brachial plexopathy was not seen in any patient. Rib fractures were noted in 6 (0.3%) patients. Late cardiac and lung toxicity was seen in 29 (1.6%) and 23 (1.3%) patients, respectively. Second malignancy developed in 105 (5.9%) patients. CONCLUSION: RNI with 40 Gy/15 fractions/3 weeks hypofractionation with 2D technique seems safe and comparable to historical data of conventional fractionation (ClinicalTrial.gov Registration No. XXXX).

Novel Mutations and Genes That Impact on Growth in Short Stature of Undefined Aetiology: The EPIGROW Study.

BACKGROUND: Children with short stature of undefined aetiology (SS-UA) may have undiagnosed genetic conditions. PURPOSE: To identify mutations causing short stature (SS) and genes related to SS, using candidate gene sequence data from the European EPIGROW study. METHODS: First, we selected exonic single nucleotide polymorphisms (SNPs), in cases and not controls, with minor allele frequency (MAF) < 2%, whose carriage fitted the mode of inheritance. Known mutations were identified using Ensembl and gene-specific databases. Variants were classified as pathogenic, likely pathogenic, or variant of uncertain significance using criteria from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. If predicted by ≥ 5/10 algorithms (eg, Polyphen2) to be deleterious, this was considered supporting evidence of pathogenicity. Second, gene-based burden testing determined the difference in SNP frequencies between cases and controls across all and then rare SNPs. For genotype/phenotype relationships, we used PLINK, based on haplotype, MAF > 2%, genotype present in > 75%, and Hardy Weinberg equilibrium P > 10-4. RESULTS: First, a diagnostic yield of 10% (27/263) was generated by 2 pathogenic (nonsense in ACAN) and a further 25 likely pathogenic mutations, including previously known missense mutations in FANCB, IGFIR, MMP13, NPR2, OBSL1, and PTPN11. Second, genes related to SS: all methods identified PEX2. Another 7 genes (BUB1B, FANCM, CUL7, FANCA, PTCH1, TEAD3, BCAS3) were identified by both gene-based approaches and 6 (A2M, EFEMP1, PRKCH, SOS2, RNF135, ZBTB38) were identified by gene-based testing for all SNPs and PLINK. CONCLUSIONS: Such panels improve diagnosis in SS-UA, extending known disease phenotypes. Fourteen genes related to SS included some known to cause growth disorders as well as novel targets.

Validation of a hierarchical algorithm to define chronic liver disease and cirrhosis etiology in administrative healthcare data.

BACKGROUND AND AIMS: Chronic liver disease (CLD) and cirrhosis are leading causes of death globally with the burden of disease rising significantly over the past several decades. Defining the etiology of liver disease is important for understanding liver disease epidemiology, healthcare planning, and outcomes. The aim of this study was to validate a hierarchical algorithm for CLD and cirrhosis etiology in administrative healthcare data. METHODS: Consecutive patients with CLD or cirrhosis attending an outpatient hepatology clinic in Ontario, Canada from 05/01/2013-08/31/2013 underwent detailed chart abstraction. Gold standard liver disease etiology was determined by an attending hepatologist as hepatitis C (HCV), hepatitis B (HBV), alcohol-related, non-alcoholic fatty liver disease (NAFLD)/cryptogenic, autoimmune or hemochromatosis. Individual data was linked to routinely collected administrative healthcare data at ICES. Diagnostic accuracy of a hierarchical algorithm incorporating both laboratory and administrative codes to define etiology was evaluated by calculating sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and kappa's agreement. RESULTS: 442 individuals underwent chart abstraction (median age 53 years, 53% cirrhosis, 45% HCV, 26% NAFLD, 10% alcohol-related). In patients with cirrhosis, the algorithm had adequate sensitivity/PPV (>75%) and excellent specificity/NPV (>90%) for all etiologies. In those without cirrhosis, the algorithm was excellent for all etiologies except for hemochromatosis and autoimmune diseases. CONCLUSIONS: A hierarchical algorithm incorporating laboratory and administrative coding can accurately define cirrhosis etiology in routinely collected healthcare data. These results should facilitate health services research in this growing patient population.

Soluble human Suppression of Tumorigenicity 2 is associated with endoscopic activity in patients with moderate-to-severe ulcerative colitis treated with golimumab.

BACKGROUND: Suppressor of Tumorigenicity 2 (ST2) is an IL33 receptor detected in the mucosa and serum of ulcerative colitis (UC) patients. We evaluated soluble ST2 (sST2) as a surrogate biomarker of disease outcome and therapeutic response, in moderate-to-severe UC patients treated with golimumab. METHODS: We conducted an open-label single-arm multicentre prospective study. At screening/baseline, week 6 (W6) and week 16 (W16), clinical and endoscopic activity (total Mayo score), histologic activity (Geboes index) and biomarkers were evaluated. RESULTS: From 38 patients, 34 (89.5%) completed W6 and 29 (76.3%) completed W16. Mean age (±SD) was 34.6 ± 12.6 years; 55.9% were female. At W16, 62.1% achieved clinical response. Patients with endoscopic activity at W6 (n = 20) had higher baseline sST2 (median, 24.5 versus 18.7 ng/ml, p = 0.026) and no decrease from baseline (median change, 0.8 versus -2.7, p = 0.029). At W6, sST2 levels correlated with endoscopic activity (rs = 0.45, p = 0.007) but not with histological activity (rs = 0.25, p = 0.151). The best cut-offs for endoscopic activity were sST2 = 16.9 ng/ml (sensitivity = 85%; specificity = 71%) and faecal calprotectin (FC) = 353 µg/g (sensitivity = 90%, specificity = 67%). Patients with histological activity at W6 (n = 27) had higher baseline ST2 levels (median, 23.0 versus 13.7 ng/ml, p = 0.035). sST2 did not correlate with FC or serum C-reactive protein. FC levels correlated with histological activity and baseline FC were higher when Geboes ⩾3.1 at W6. CONCLUSIONS: sST2 may be a surrogate biomarker of UC activity and therapeutic response as it correlates with endoscopic and clinical activity at W6 of golimumab treatment, and subjects with endoscopic and histological activity at W6 had higher baseline ST2 levels.

Early Dose Optimisation of Golimumab in Nonresponders to Induction Treatment for Ulcerative Colitis Is Effective and Supported by Pharmacokinetic Data.

BACKGROUND AND AIMS: In nonresponders to golimumab induction for ulcerative colitis, we assessed clinical response rates and golimumab serum concentrations when the 100-mg dose was used early in the course of maintenance. METHODS: This post-hoc analysis of golimumab maintenance dosing [in the PURSUIT-M study] examined clinical outcomes and golimumab concentrations in early [Week 6] responders and nonresponders to induction, including subgroups based on body weight. RESULTS: In nonresponders to golimumab induction [assessed at Week 6], the 100-mg maintenance dose [starting at Week 6] resulted in a meaningful proportion [28.1%] of patients achieving a partial Mayo response at Week 14. After 1 year of maintenance, clinical outcome [response, remission, mucosal healing, corticosteroid-free state] rates in these "late" [Week 14] responders were similar to those in early [Week 6] responders. Golimumab concentrations in early nonresponders were approximately half those of early responders, suggesting that early nonresponders had more rapid golimumab clearance. Examined by body weight, the early nonresponders weighing <80 kg and receiving 100 mg had golimumab concentrations similar to the early responders [weighing <80 kg or ≥80 kg and receiving 50 mg or 100 mg, respectively]. CONCLUSIONS: Early use of the 100-mg maintenance dose leads to positive clinical outcomes in a meaningful proportion of patients who did not respond to golimumab at Week 6. Early nonresponders <80 kg who received the 100-mg maintenance dose achieved adequate golimumab concentrations and a clinically meaningful proportion of these patients had a late clinical response.PURSUIT-M protocol number C0524T18; ClinicalTrials.gov, NCT00488631; EudraCT, 2006-003399-37.

Five-year Safety Data From OPUS, a European Observational Safety Registry for Adults With Ulcerative Colitis Treated With Originator Infliximab [Remicade®] or Conventional Therapy.

BACKGROUND AND AIMS: The Observational Postmarketing Ulcerative colitis Study [OPUS] was conducted to obtain the first long-term [5 years] safety data assessing treatment with originator infliximab versus conventional therapies in patients with ulcerative colitis [UC] in real-world clinical practice. METHODS: The OPUS registry was a prospective, non-randomised, observational study that measured adverse events in nine prespecified categories of interest in UC patients whose treatment with either originator infliximab or conventional therapy [defined as initiation or dose-increase of corticosteroids and/or immunosuppressants] was determined by their treating physician. RESULTS: Data for 2239 patients were available: N = 1180 enrolled to conventional therapy [including N = 296 who switched to originator infliximab during follow-up] and N = 1059 enrolled to originator infliximab. Patients in the originator infliximab group, compared with the conventional therapy group, had more severe disease at baseline, based on partial Mayo score [PMS]: 46.0% of patients in the originator infliximab group had severe disease (PMS of 7-9 [out of 9]), compared with 30.5% in the conventional therapy group. In adjusted time-to-event analyses, enrolment into the originator infliximab group was associated with a higher risk of serious infection (hazard ratio = 1.98 [95% confidence interval: 1.34, 2.91; p <0.001]) compared with enrolment into the conventional therapy group. No notable risk differences between groups were identified for haematological disorder, autoimmune disorder, malignancy/lymphoproliferative disorder, hepatobiliary disorder or fatality. CONCLUSIONS: UC patients treated with infliximab had higher risk for serious infection, compared with conventional therapies. No new safety concerns were observed with originator infliximab in the OPUS registry. [ClinicalTrials.gov: NCT00705484.].

PIK3CA mutation in a mixed dysembryoplastic neuroepithelial tumor and rosette forming glioneuronal tumor, a case report and literature review.

BACKGROUND: Rosette forming glioneuronal tumors are rare, World Health Organization (WHO) grade I novel tumors frequently affecting the fourth ventricle or posterior fossa with typical neuronal pseudorosettes. RGNTs have been described as possessing additional histologic features of DNETs or pilocytic astrocytomas. Activating PIK3CA mutations have been identified as recurring genetic event in RGNTs. METHODS: We report a 35year old man who presented with binocular diplopia, headache, and was found to have a third ventricle tumor. Tumor pathology and oncogene evaluation were conducted. RESULTS: The tumor demonstrated histologic features consistent with mixed RGNT/DNET. Genetic studies revealed a PIK3CA mutation in exon 9 (E545K, C. 1633G>A) without IDH1, p53, 1p19q chromosomal co-deletion, or BRAF mutations. A literature search revealed six cases of PIK3CA mutations in RGNTs and seven cases of mixed RGNT/DNET. No cases of mixed RGNT/DNET with a PIK3CA mutation have been described. CONCLUSION: This is the first documented case of an RGNT/DNET with an activating PIK3CA mutation. The presence of a PIK3CA mutation aids histologic classification in the setting of mixed histology, and may have implications for targeting the PI3K/AKT/mTOR pathway in this tumor type.

Validity of tuberculous pleuritis diagnosed in a resource-constrained setting in Dindigul district of Tamil Nadu.

CONTEXT: Majority of the Indians live in rural areas where resource constrained settings depend on cheaper and less invasive tests to diagnose extrapulmonary tuberculosis (TB). The decline in prevalence of TB in the country could affect the validity of the diagnosis. The aim was to measure validity of the pleural fluid study of proteins, lactate dehydrogenase (LDH), and cell counts in diagnosis of tuberculous pleuritis. MATERIALS AND METHODS: This was a cross-sectional study conducted in a 300 bedded secondary care hospital in rural Tamil Nadu. Exhaustive sampling was performed during April 2013 to March 2014. Pleural fluid study of 54 patients with exudative pleural effusion was conducted. Diagnosis was established by closed needle pleural biopsy. Receiver operator curves were plotted and area under curve (AUC) was calculated for various parameters. Sensitivity, specificity, and predictive values were calculated for different cut-off values of the parameter with significant AUC. RESULTS: Prevalence of tuberculous pleural effusion was 56% (95% confidence interval [95% CI] - 42.5-69.5%). Lymphocyte predominance in pleural fluid was the only valid test, and cut-off >80% had sensitivity of 70.0% (95% CI - 53.3-86.7%) and specificity of 70.8% (95% CI - 52.2-89.4%). Pleural fluid pH, protein or its ratio with serum protein, sugar, total leukocyte count, LDH or its ratio with serum LDH; erythrocyte sedimentation rate were not valid screening tests. CONCLUSIONS: Lymphocyte predominance > 80% can be used as a marker of tuberculous pleuritis. Since the prevalence of tuberculous pleuritis in India has come down considerably, newer tests need to be included to make a valid diagnosis.

A case report of peritoneal malignant mesothelioma presenting as primary ovarian mass.

Malignant mesotheliomas are aggressive neoplasms arising from mesothelial cells lining the body cavities. Malignant peritoneal mesothelioma (MPM) account for about one-third of the cases. Though the ovarian involvement may be seen in the background of a diffuse peritoneal involvement, the presentation of MPM as a primary ovarian mass is rare. Here we present such a case who underwent surgery but had residual progressive lesion. She received further chemotherapy resulting in a complete response and is disease free for almost a year.

Gossypiboma mimicking a retroperitoneal tumor.

"Gossypiboma" denotes a mass of cotton that is retained in the body after surgery. An image is presented of a retroperitoneal mass in a lady who had a right nephrectomy 8 years earlier for a nonfunctioning kidney. Clinical examination and plain abdominal radiography were not contributory. Contrast-enhanced abdominal computed tomography revealed a well-defined, heterogeneous, spherical, soft-tissue mass, 13 × 9 × 9 cm in size, in the retroperitoneum, with a dense enhanced wall, abutting the right psoas and posterior abdominal wall. Exploration revealed an abdominal sponge surrounded by foreign body granuloma adherent to surrounding structures. Gossypiboma can mimic a tumor and is a diagnostic challenge.

Brown tumor and staghorn calculi in primary hyperparathyroidism.

A case of primary hyperparathyroidism with bilateral renal staghorn calculi and brown tumor right thumb is reported in these images, along with the appropriate sequential management. Percutaneous nephrolithotomy (PCNL)was done after management of hypercalcemia and after parathyroidectomy. This case highlights the need for urologists and general practitioners to have a holistic approach in patient management.

Effect of montelukast for treatment of asthma in cigarette smokers.

OBJECTIVE: Many asthmatic patients are unable to quit cigarettes; therefore information is needed on treatment options for smokers. This study evaluates 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily, each compared with placebo, in patients with self-reported active smoking (unable to quit) and asthma. METHODS: Patients (ages 18-55 years, with asthma [≥1 year], FEV1 of 60% to 90% of predicted value, airway reversibility [≥12%], and self-reported active smoking [≥0.5 to ≤2 packs per day]) were randomized (after a 3-week, single-blind, placebo, run-in period) to 1 of 3 parallel, 6-month, double-blind treatment arms. The primary efficacy end point was the percentage of days with asthma control during treatment. Adverse experiences (AEs) were also evaluated. RESULTS: There were 347, 336, and 336 patients randomized to montelukast, fluticasone, and placebo, respectively. The mean percentage of days with asthma control over 6 months of treatment was 45% (montelukast, P < .05 vs placebo), 49% (fluticasone, P < .001 vs placebo), and 39% (placebo); the difference between montelukast and fluticasone was not significant (P = .14). Patients with a smoking history of ≤11 pack years (the median value) tended to show more benefit with fluticasone, whereas those with a smoking history of >11 pack years tended to show more benefit with montelukast. AEs occurred in similar proportions among treatment groups. CONCLUSIONS: In a population of asthmatic patients actively smoking cigarettes, both 10 mg/d montelukast and 250 µg of fluticasone propionate twice daily significantly increased the mean percentage of days with asthma control compared with placebo.

Randomized controlled trial evaluating the clinical benefit of montelukast for treating spring seasonal allergic rhinitis.

BACKGROUND: Symptoms of allergic rhinitis are mediated in part by cysteinyl leukotrienes. OBJECTIVE: To evaluate the clinical benefit of montelukast, a cysteinyl leukotriene receptor antagonist, administered once daily for treating seasonal allergic rhinitis. METHODS: This multicenter, randomized, double-blind, placebo- and active-controlled study enrolled 1,214 healthy, nonsmoking outpatients aged 15 to 85 years with spring allergic rhinitis, positive skin test to a spring allergen, and predefined daytime nasal symptoms. After a 3- to 5-day placebo run-in period, patients were randomly assigned to treatment with montelukast 10 mg (n = 522), loratadine 10 mg (n = 171), or placebo (n = 521) once daily at bedtime for 2 weeks. During the run-in and treatment periods, symptoms were evaluated in a daily diary using a 0 (best) to 3 (worst) scale. RESULTS: Baseline characteristics of randomized patients were clinically similar in the three treatment groups. Montelukast was significantly more effective than placebo (P = 0.003) in improving the daytime nasal symptoms score (difference in least square means, -0.09; 95% confidence interval, -0.16, -0.03) averaged over 2 weeks of therapy. The treatment effect of montelukast was significantly greater (P < 0.05), relative to placebo, for all secondary endpoints, including nighttime symptoms and daytime eye symptoms, patient and physician global evaluations of allergic rhinitis, and rhinoconjunctivitis quality of life. Loratadine, which served as a positive control, was significantly more effective than placebo for most endpoints, validating the study results. Both montelukast and loratadine were well tolerated. CONCLUSION: Therapy with montelukast significantly improves assessments of symptom severity as well as quality-of-life parameters for patients with seasonal allergic rhinitis.

Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicenter, randomized, double-blind, placebo-controlled trial performed in the fall.

BACKGROUND: Histamine and cysteinyl leukotrienes seem to be important mediators of allergic rhinitis. OBJECTIVE: This multicenter, randomized, double-blind, parallel-group, placebo-controlled trial evaluated the effectiveness and tolerability of montelukast, loratadine, and combination therapy with montelukast and loratadine for treating patients with fall seasonal allergic rhinitis. METHODS: After a 1-week, single-blind, placebo run-in period, 907 male and female patients aged 15 to 82 years were randomized to 1 of 4 treatments: montelukast 10 mg (n = 155), loratadine 10 mg (n = 301), combination montelukast 10 mg and loratadine 10 mg (n = 302), or placebo (n = 149), administered once daily at bedtime for 2 weeks. The primary endpoint was the daytime nasal symptoms score (mean of congestion, rhinorrhea, pruritus, and sneezing). RESULTS: Mean symptom scores at baseline were similar for the four treatment groups. For each of the three active treatments, the difference was significant for the mean change from baseline compared with placebo (P < or = 0.001). However, the effect of montelukast/loratadine compared with loratadine alone, the primary comparison, was not significantly different. Differences for each therapy alone compared with placebo were also significant for most secondary endpoints, including nighttime symptom scores, eye symptoms scores, and rhinitis-specific quality of life. Differences for montelukast/loratadine compared with each therapy alone generally showed numerical superiority, and a few endpoints showed differences that were statistically significant. All active treatments showed a safety profile generally similar to placebo. CONCLUSIONS: Montelukast alone or in combination with loratadine is well tolerated and provides clinical and quality-of-life benefits for patients with seasonal allergic rhinitis.