Disclosure of Funding Sources and Conflicts of Interest in Phase III Surgical Trials: Survey of Ten General Surgery Journals

Background

Discussions regarding disclosure of funding sources and conflicts of interest (COI) in published peer-reviewed journal articles are becoming increasingly more common and intense. The aim of the present study was to examine whether randomized controlled trials (RCTs) published in leading surgery journals report funding sources and COI.

Methods

All articles reporting randomized controlled phase III trials published January 2005 through December 2010 were chosen for review from ten international journals. We evaluated the number of disclosed funding sources and COI, and the factors associated with such disclosures.

Results

From a review of 657 RCT from the ten journals, we discovered that presence or absence of a funding source and COI was disclosed by 47 % (309) and 25.1 % (165), respectively. Most articles in “International Committee of Medical Journal Editors (ICMJE)-affiliated journals” did not disclose COI. Disclosure of funding was associated with a journal impact factor >3 (51.7 vs 41.6 %; p < 0.01), statistician/epidemiologist involvement (64.2 vs 43.7 %; p < 0.001), publication after 2008 (52.9 vs 41.1 %; p < 0.01), and the journal being ICMJE-affiliated (49.3 vs 40 %; p < 0.05). Conflict of interest disclosure was associated with publication after 2008 (38.7 vs 11.3 %; p < 0.001), and with the journal not being affiliated with ICMJE (36.9 vs 21.3 %; p < 0.001).

Conclusions

Of the published studies we investigated, over half did not disclose funding sources (i.e., whether or not there was a funding source), and almost three quarters did not disclose whether COI existed. Our findings suggest the need to adopt best current practices regarding disclosure of competing interests to fulfill responsibilities to readers and, ultimately, to patients.     

Trends in epidemiology and patho-anatomical pattern of proximal humeral fractures

Purpose

Proximal humeral fractures are common and frequently associated with osteoporosis. Little is known about the association between the patho-anatomical fracture pattern of proximal humeral fractures and patient characteristics. The purpose of this six year longitudinal registry analysis of proximal humeral fractures was to study overall numbers, certain predefined pathoanatomical patterns and distribution compared with specific patient characteristics.

Methods

Data of patients treated between 2006 and 2011 in a country hospital that provides care >95 % of the city’s hospitalised patients with fractures was retrospectively reviewed. Data were analysed according to patient characteristics of age, gender, comorbidity, accompanying injuries and radiological analysis of pathoanatomical fracture patterns based on Neer and Arbeitsgemeinschaft für Osteosynthesefragen (AO) classification.

Results

Eight hundred and fifteen proximal humeral fractures (67 % women/33 % men; mean age 66 years, range 19–99) were analysed. During the study period, an overall increase of 42.5 % was found: according to AO classification, 46 % were type A, 22 % type B and 32 % type C. Based on the Neer classification, 86 % were displaced, and 49 % were complex with more than three parts. Of complex fractures, 57 % were female patients >60 years. The number of complex fractures was five times higher in women >60 years than in men of the same age group.

Conclusions

An overall increase of inpatients with displaced proximal tibial fractures was documented. Interestingly, complex displaced proximal humeral fractures, especially in older women with comorbidities, accounted for the majority of cases. These results suggest that health-care planning and hospital-based therapeutic strategies should focus on this patient group.     

The hypothalamic–pituitary–gonadal axis and prostate cancer: implications for androgen deprivation therapy

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) may play important roles in prostate cancer (PCa) progression. Specifically, LH expression in PCa tissues has been associated with metastatic disease with a poor prognosis, while FSH has been shown to stimulate prostate cell growth in hormone-refractory PCa cell lines. Gonadotropin-realizing hormone (GnRH) analogues are common agents used for achieving androgen deprivation in the treatment for PCa. GnRH analogues include LH-releasing hormone (LHRH) agonists and GnRH antagonists, both of which exhibit distinct mechanisms of action that may be crucial in terms of their overall clinical efficacy. LHRH agonists are typically used as the primary therapy for most patients and function via a negative-feedback mechanism. This mechanism involves an initial surge in testosterone levels, which may worsen clinical symptoms of PCa. GnRH antagonists provide rapid and consistent hormonal suppression without the initial surge in testosterone levels associated with LHRH agonists, thus representing an important therapeutic alternative for patients with PCa. The concentrations of testosterone and dihydrotestosterone are significantly reduced after treatment with both LHRH agonists and GnRH antagonists. This reduction in testosterone concentrations to castrate levels results in significant, rapid, and consistent reductions in prostatic-specific antigen, a key biomarker for PCa. Evidence suggests that careful maintenance of testosterone levels during androgen deprivation therapy provides a clinical benefit to patients with PCa, emphasizing the need for constant monitoring of testosterone concentrations throughout the course of therapy.     

Prospective evaluation of intra-observer variability of the hydronephrosis index in sonographic examination of 44 patients with acute renal colic

Purpose

The aim of our prospective designed study was to confirm the intra-observer agreement of assessments of the hydronephrosis index (HI) with a sonographic technique that potentially provides additional information in patients with acute renal colic (ARC).

Methods

Sonographic measurement of HI and valuation of common clinical criteria were performed in 44 consecutive patients presenting with unilateral stone-related ARC. HI of colic side was recorded twice in predefined time intervals. Intra-observer agreement was evaluated with the Spearman’s rank correlation/rho (ρ) for attributive-metric characteristics. Data of HI-measurement on the colic side were compared with data of the unaffected side using t test.

Results

Intra-observer agreement was significant for HI in the colic side (ρ = 0.918, p < 0.001) and in the unaffected side (ρ = 0.826, p < 0.001). The mean HI between colic and unaffected side differed significantly on the first evaluation (85.2 vs. 93.7, respectively; p < 0.001) and on the second evaluation (85.1 vs. 93.6, respectively; p < 0.001) as well.

Conclusions

The HI method is a slightly feasible examination method in patients presenting with stone-related renal colic. Moreover, it offers a solid discrimination between obstruction and non-obstruction. Our prospective trial illustrates HI as a reproducible method with a high-grade intra-observer agreement. However, potential change of values under medical expulsive therapy and coherency with the functionality of the obstructed kidney may lead to bias and therefore remain to be analyzed. Further studies to specify exact thresholds for this method and to state our findings are required.     

Multidisciplinary Treatment in Patients With Persistent Pain Following Total Hip and Knee Arthroplasty

In a retrospective study, we evaluated the clinical outcome of multidisciplinary pain therapy (MPT) in a consecutive series of 40 patients with persistent unexplained pain following THA or TKA. Pain intensity, physical capability and psychological status were assessed before MPT (t1), after 3 weeks (t2) and at a mean follow-up of 32 months (t3). At t2, all scores demonstrated a significant improvement compared to the baseline value. At t3, pain intensity, physical capability, and depression levels deteriorated slightly but were still significantly better compared to baseline values. Anxiety scores deteriorated between t2 and t3 and showed no difference in the baseline value. The present study suggests that MPT has beneficial short-term and mid-term effects in this subgroup of patients and may avoid exploratory revision surgery.     

Greater Prevalence of Wound Complications Requiring Reoperation With Direct Anterior Approach Total Hip Arthroplasty

The purpose of this retrospective study was to compare wound complication rates between primary THAs performed via a posterior or direct anterior approach. From our prospective outcomes registry, we identified 1288 primary THAs performed via a posterior approach and 505 via a direct anterior approach. The direct anterior approach resulted in a significantly greater number of wound complications that required reoperation than the posterior approach (7/505 (1.4%) vs. 3/1,288 (0.2%), P = 0.007). As such, patients should be counseled on the potential increased risk of early wound complications with the direct anterior approach, and future research is needed to determine if alternative closure techniques can reduce the risk of wound complication.     

Autologous protein solution prepared from the blood of osteoarthritic patients contains an enhanced profile of anti‐inflammatory cytokines and anabolic growth factors

The objective of this clinical study was to test if blood from osteoarthritis (OA) patients (n = 105) could be processed by a device system to form an autologous protein solution (APS) with preferentially increased concentrations of anti‐inflammatory cytokines compared to inflammatory cytokines. To address this objective, APS was prepared from patients exhibiting radiographic evidence of knee OA. Patient metrics were collected including: demographic information, medical history, medication records, and Knee Injury and Osteoarthritis Outcome Score (KOOS) surveys. Cytokine and growth factor concentrations in whole blood and APS were measured using enzyme‐linked immunosorbent assays. Statistical analyses were used to identify relationships between OA patient metrics and cytokines. The results of this study indicated that anti‐inflammatory cytokines were preferentially increased compared to inflammatory cytokines in APS from 98% of OA patients. APS contained high concentrations of anti‐inflammatory proteins including 39,000 ± 20,000 pg/ml IL‐1ra, 21,000 ± 5,000 pg/ml sIL‐1RII, 2,100 ± 570 pg/ml sTNF‐RI, and 4,200 ± 1,500 pg/ml sTNF‐RII. Analysis of the 82 patient metrics indicated that no single patient metric was strongly correlated (R² > 0.7) with the key cytokine concentrations in APS. Therefore, APS can be prepared from a broad range of OA patients. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1349–1355, 2014.     

Relationship between muscle fatty infiltration and the biological characteristics and stimulation potential of tenocytes from rotator cuff tears

The healing after rotator cuff surgery is still dissatisfying, and increased muscle fatty infiltration even more impairs the healing success. To achieve sufficient healing after rotator cuff reconstructions, the use of growth factors may be one possibility. The aim of the study was to identify a possible relationship between fatty infiltration of the supraspinatus muscle and cellular biological characteristics and stimulation potential of tenocyte‐like cells (TLCs). TLCs of 3 donor groups differing in grade of muscle fatty infiltration were analyzed for their cellular characteristics and were stimulated with BMP‐2 or BMP‐7 in a 3D scaffold culture. The cell count and potency for self‐renewal were significantly decreased in TLCs from donors with high muscle fatty infiltration compared to the lower fatty infiltration groups. Cell count and collagen‐I expression as well as protein synthesis were stimulated by growth factors. Interestingly, TLCs of the high fatty infiltration group exhibited a weaker stimulation potential compared to the other groups. TLCs from donors with high muscle fatty infiltration generally revealed inferior characteristics compared to cells of lower fatty infiltration groups, which may be one reason for a weaker healing potential and may represent a possible starting point for the development of future treatment options. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:129–137, 2014.