Comments on the efficacy and safety of opioid analgesics for the management of chronic low back pain

To the editor: With great interest we have read the article written by Boya et al. This was a systematic review and network meta-analysis in which opioids were ranked on efficacy and safety for the treatment of chronic low back pain (CLBP). The authors concluded that oxymorphone is the most effective opioid, and hydromorphone is the safest. However, as mentioned by the authors, oxymorphone recently had its United States (U.S.) Food and Drug Administration (FDA)-approval withdrawn because of its misuse. This points to the reason why we are writing this letter.[...

Colorimetric Detection of Uranyl Using a Litmus Test

Ingestion of water containing toxic contaminants above levels deemed safe for human consumption can occur unknowingly since numerous common contaminants in drinking water are colorless and odorless. Uranyl is particularly problematic as it has been found at dangerous levels in sources of drinking water. Detection of this heavy metal-ion species in drinking water currently requires sending a sample to a laboratory where trained personnel use equipment to perform the analysis and turn-around times can be long. A pH-responsive colorimetric biosensor was developed to enable detection of uranyl in water which coupled the uranyl-specific 39E DNAzyme as a recognition element, and an enzyme capable of producing a pH change as the reporter element. The rapid colorimetric assay presented herein can detect uranyl in lake and well water at concentrations relevant for environmental monitoring, as demonstrated by the detection of uranyl at levels below the limits set for drinking water by major regulatory agencies including the World Health Organization (30 μg/L). This simple and inexpensive DNAzyme-based assay enabled equipment-free visual detection of 15 μg/L uranyl, using both solution-based and paper-based pH-dependent visualization strategies

Concurrent validity and reliability of a semi-automated approach to measuring the magnetic resonance imaging morphology of the knee joint in active youth

Post-traumatic knee osteoarthritis is attributed to alterations in joint morphology, alignment, and biomechanics triggered by injury. While magnetic resonance (MR) imaging-based measures of joint morphology and alignment are relevant to understanding osteoarthritis risk, time consuming manual data extraction and measurement limit the number of outcomes that can be considered and deter widespread use. This paper describes the development and evaluation of a semi-automated software for measuring tibiofemoral and patellofemoral joint architecture using MR images from youth with and without a previous sport-related knee injury. After prompting users to identify and select key anatomical landmarks, the software can calculate 37 (14 tibiofemoral, 23 patellofemoral) relevant geometric features (morphology and alignment) based on established methods. To assess validity and reliability, 11 common geometric features were calculated from the knee MR images (proton density and proton density fat saturation sequences; 1.5 T) of 76 individuals with a 3-10-year history of youth sport-related knee injury and 76 uninjured controls. Spearman's or Pearson's correlation coefficients (95% CI) and Bland-Altman plots were used to assess the concurrent validity of the semi-automated software (novice rater) versus expert manual measurements, while intra-class correlation coefficients (ICC 2,1; 95%CI), standard error of measurement (95%CI), 95% minimal detectable change, and Bland-Altman plots were used to assess the inter-rater reliability of the semi-automated software (novice vs resident radiologist rater). Correlation coefficients ranged between 0.89 (0.84, 0.92; Lateral Trochlear Inclination) and 0.97 (0.96, 0.98; Patellar Tilt Angle). ICC estimates ranged between 0.79 (0.63, 0.88; Lateral Patellar Tilt Angle) and 0.98 (0.95, 0.99; Bisect Offset). Bland-Altman plots did not reveal systematic bias. These measurement properties estimates are equal, if not better than previously reported methods suggesting that this novel semi-automated software is an accurate, reliable, and efficient alternative method for measuring large numbers of geometric features of the tibiofemoral and patellofemoral joints from MR studies. </p

Patellofemoral joint geometry and osteoarthritis features 3–10 years after knee injury compared with uninjured knees

In this cross-sectional study, we compared patellofemoral geometry in individuals with a youth-sport-related intra-articular knee injury to uninjured individuals, and the association between patellofemoral geometry and magnetic resonance imaging (MRI)-defined osteoarthritis (OA) features. In the Youth Prevention of Early OA (PrE-OA) cohort, we assessed 10 patellofemoral geometry measures in individuals 3–10 years following injury compared with uninjured individuals of similar age, sex, and sport, using mixed effects linear regression. We also dichotomized geometry to identify extreme (&gt;1.96 standard deviations) features and assessed likelihood of having extreme values using Poisson regression. Finally, we evaluated the associations between patellofemoral geometry with MRI-defined OA features using restricted cubic spline regression. Mean patellofemoral geometry did not differ substantially between groups. However, compared with uninjured individuals, injured individuals were more likely to have extremely large sulcus angle (prevalence ratio [PR] 3.9 [95% confidence interval, CI: 2.3, 6.6]), and shallow lateral trochlear inclination (PR 4.3 (1.1, 17.9)) and trochlear depth (PR 5.3 (1.6, 17.4)). In both groups, high bisect offset (PR 1.7 [1.3, 2.1]) and sulcus angle (PR 4.0 [2.3, 7.0]) were associated with cartilage lesion, and most geometry measures were associated with at least one structural feature, especially cartilage lesions and osteophytes. We observed no interaction between geometry and injury. Certain patellofemoral geometry features are correlated with higher prevalence of structural lesions compared with injury alone, 3–10 years following knee injury. Hypotheses generated in this study, once further evaluated, could contribute to identifying higher-risk individuals who may benefit from targeted treatment aimed at preventing posttraumatic OA.</p

Physical and psychosocial work-related exposures and the occurrence of disorders of the shoulder:A systematic review update

This review is an update of a previous systematic review and assesses the evidence for the association of work-related physical and psychosocial risk factors and specific disorders of the shoulders. Medline, Embase, Web of Science Core Collection, Cochrane Central and PsycINFO were searched and study eligibility and risk of bias assessment was performed by two independent reviewers. A total of 14 new articles were added with the majority focusing on rotator cuff syndrome (RCS) with seven studies. Nine articles reported psychosocial exposures in addition to physical exposures. The strongest evidence was found for the association between elevation, repetition, force and vibration and the occurrence of SIS and tendinosis/tendonitis. Evidence also suggests that psychosocial exposures are associated with the occurrence of RCS and tendinosis/tendonitis. Other findings were inconsistent which prevents drawing strong conclusions.</p

Novel Marmoset (Callithrix jacchus) Model of Human Herpesvirus 6A and 6B Infections: Immunologic, Virologic and Radiologic Characterization

Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders