Management of Patients With High Baseline Hip Fracture Risk by FRAX Reduces Hip Fractures—A Post Hoc Analysis of the SCOOP Study

The Screening for Osteoporosis in Older Women for the Prevention of Fracture (SCOOP) study was a community‐based screening intervention in women aged 70 to 85 years in the United Kingdom. In the screening arm, licensed osteoporosis treatments were recommended in women identified to be at high risk of hip fracture using the FRAX risk assessment tool (including bone mineral density measurement). In the control arm, standard care was provided. Screening led to a 28% reduction in hip fractures over 5 years. In this planned post hoc analysis, we wished to examine for interactions between screening effectiveness on fracture outcome (any, osteoporotic, and hip fractures) on the one hand and baseline FRAX 10‐year probability of hip fracture on the other. All analyses were conducted on an intention‐to‐treat basis, based on the group to which women were randomized, irrespective of whether screening was completed. Of 12,483 eligible participants, 6233 women were randomized to screening, with treatment recommended in 898 (14.4%). No evidence of an effect or interaction was observed for the outcomes of any fracture or osteoporotic fracture. In the screening arm, 54 fewer hip fractures were observed than in the control arm (164 versus 218, 2.6% versus 3.5%), and commensurate with treatment being targeted to those at highest hip fracture risk, the effect on hip fracture increased with baseline FRAX hip fracture probability (p = 0.021 for interaction); for example, at the 10th percentile of baseline FRAX hip probability (2.6%), there was no evidence that hip fractures were reduced (hazard ratio [HR] = 0.93; 95% confidence interval [CI] 0.71 to 1.23), but at the 90th percentile (16.6%), there was a 33% reduction (HR = 0.67; 95% CI 0.53 to 0.84). Prior fracture and parental history of hip fracture positively influenced screening effectiveness on hip fracture risk. We conclude that women at high risk of hip fracture based on FRAX probability are responsive to appropriate osteoporosis management. © 2018 American Society for Bone and Mineral Research.     

Differential expression of HLA-DR antigens in subsets of human CFU-GM

Expression of HLA-DR surface antigens by granulocyte/monocyte colony- forming cells (CFU-GM) may be important in the regulation of proliferation of these cells. Using immunological techniques to enrich for progenitor cells, we investigated the expression of HLA-DR in subsets of CFU-GM. "Early" (day 14) CFU-GM express higher levels of HLA- DR than do "late" (day 7) CFU-GM. Among late CFU-GM, cells destined to form monocyte (alpha-naphthyl acetate esterase-positive) colonies express higher levels of HLA-DR than do CFU-GM destined to form granulocyte (chloroacetate esterase-positive) colonies. Because high- level expression of DR antigen was a marker for monocyte differentiation, we examined several lymphokines for their effects on both DR expression and in vitro commitment to monocyte differentiation by myeloid precursor cells. DR antigen density could be increased by more than twofold over 48 hours upon exposure to gamma-interferon (gamma-IFN), whereas colony-stimulating factors had no effect. This was associated with a dose-dependent inhibition of total CFU-GM number, and a relative, but not absolute, increase in the ratio of monocyte colonies to granulocyte colonies. Similarly, in day 7 suspension cultures of purified myeloid precursor cells, gamma-IFN inhibited cell proliferation and increased the ratio of monocytes to granulocytes. Thus, despite the induction of high levels of HLA-DR antigen on precursor cells (a marker of monocyte commitment), the dominant in vitro effect of gamma-IFN was inhibition of granulocyte differentiation.     

Validity of the new A1 and A2 criteria for DSM-5 intermittent explosive disorder

A disorder of impulsive aggression has been in the Diagnostic and Statistical Manual for Mental Disorders (DSM) since the first edition. In DSM-III, this disorder was codified as Intermittent Explosive Disorder (IED) and was thought to be rare. However, DSM criteria for IED were poorly operationalized and empiric research in IED was limited until the past decade when research criteria were developed. Subsequently, renewed interest in disorders of impulsive aggression led to a recent series of community based studies that have now documented IED to be as common as many other psychiatric disorders. Recent research indicates that the core of IED (A criteria) can be captured with new criteria that identify high frequency/low intensity aggressive outbursts (A₁) and low frequency/hi intensity outbursts (A₂). This paper presents new data regarding the phenomenology, comorbidity/life course of IED as a function of A₁ and A₂ criteria. Together with reanalysis of previously published data regarding family history, biomarkers, and treatment response in individuals with recurrent, problematic, impulsive aggression, these data provide empirical support for both A₁ and A₂ criteria for DSM-5 IED.     

Morphology and localization of interstitial cells in the guinea pig bladder: structural relationships with smooth muscle and neurons

PURPOSE: In the current study we examined the location of interstitial cell of Cajal (ICC)-like cells in the guinea pig bladder wall and studied their structural interactions with nerves and smooth muscle cells. MATERIALS AND METHODS: Whole mount samples and cryosections of bladder tissue were labeled with primary and fluorescent secondary antibodies, and imaged using confocal and multiphoton microscopy. RESULTS: Kit positive ICC-like cells were located below the urothelium, in the lamina propria region and throughout the detrusor. In the suburothelium they had a stellate morphology and appeared to network. They made connections with nerves, as shown by double labeling experiments with anti-kit and anti-protein gene product 9.5. A network of vimentin positive cells was also found, of which many but not all were kit positive. In the detrusor kit positive cells were most often seen at the edge of smooth muscle bundles. They were elongated with lateral branches, running in parallel with the bundles and closely associated with intramural nerves. Another population of kit positive cells was seen in the detrusor between muscle bundles. These cells had a more stellate-like morphology and made connections with each other. Kit positive cells were seen tracking nerve bundles and close to intramural ganglia. Vimentin positive cells were present in the detrusor, of which some were also kit positive. CONCLUSIONS: There are several populations of ICC-like cells throughout the guinea pig bladder wall. They differ in morphology and orientation but all make connections with intramural nerves and in the detrusor they are closely associated with smooth muscle cells.     

Informed consent for intravascular administration of contrast material: how much is enough?

To determine the usefulness of informed consent prior to the intravascular administration of contrast material, the authors evaluated four equal groups of patients with different degrees of counseling concerning risks and risk factors. Group 1 was given no information. Group 2 was informed of the common risks in a written statement. Group 3 was informed of all known risks in a written statement. Group 4 was informed of all known risks by means of physician counseling. The average times it took for the technologist (groups 1-3) or the physician (group 4) to counsel the patient and obtain informed consent were 1.7, 6.2, 13.6, and 11.4 minutes, respectively. Counseling by physicians would require approximately 7% of their professional time in a busy radiology department. On a postprocedure test, the patients in groups 1-4 scored on average 38.4%, 68.2%, 63.2%, and 69.8%, respectively. There was no statistical difference in the performance of groups 2-4 on the postprocedure test. If informed consent is to be obtained prior to intravascular administration of contrast material, use of a straightforward written consent form detailing the common risks and risk factors appears to be the best method.