Consequences of the widespread use of antibiotics

The cancer problem is increasing as life expectancy increases and greater portions of the populace live to the age at which cancer is more likely. Early diagnosis still is difficult. Even with modern methods and with considerable public education with regard to cancer, the disease is often not diagnosed until it is beyond the stage at which cure might be effected. The need for a serodiagnostic test for general screening purposes for cancer detection is tremendous. The major objective of cancer serodiagnostic test methods is to discover a general test that will detect cancer in a high percentage of cases while it is in an early stage; that will give few "false positive" results; that can be done in any laboratory; and that is simple and inexpensive. Many serodiagnostic tests for cancer have been published but none has proven worthy of being a good general test to detect cancer. Yet unless some serodiagnostic test which will be suitable for general screening purposes is developed, it is difficult to see how there can be much improvement in the early diagnosis of cancer, particularly internal cancer. It is hoped that an open-minded attitude will be maintained by physicians on this subject. Recent reports of such a test being developed are encouraging and it is hoped that continued investigations will be confirmatory.     

Predicting fracture of the femoral neck

A prediction of the probability of safe loading of the femoral neck, based on queueing theory, is presented. The following methods have been applied: (I) criterion of bone fracture was formulated, taking into consideration the complex state of stress-strain in the porosity zones of the bone; (II) tensile stresses around pores in the stretched zone of the bone were evaluated; (III) the influence of random events of the critical regimes of loading was modeled. The evaluation of the probability of safe loading of bones was obtained based on the levels of the tensile stresses, Young's moduli and ultimate tensile stresses which are affected by the increase in bone porosity and the distribution of the pores. Examples of analysis involving typical mechanical properties of bone in areas of vascular and lacunar-canalicular porosity are demonstrated. The ranges of initial average values of effective Young's moduli and ultimate tensile strengths were taken as 15.8-17.5GPa and 83-95MPa, respectively. The present analysis discovers the existence of three levels of safe loading: (1) a relatively safe level of the nominal tensile stresses (smaller than (2.8-3.2)MPa) where the probability of safe loading is of the order of 0.95 for the bone porosity which is less than 0.15; (2) an intermediate level of safety where the nominal tensile stresses are below (4.2-4.8)MPa and the probability of safe loading is 0.89 or higher, for the same level of bone porosity; (3) a critical level of safe loading where the nominal tensile stresses are about (8.3-9.5)MPa; they lead to sharp drop of probabilities of safe loading to 0.85-0.8 if the porosity is about 0.10 and to probabilities of 0.41-0.4 if the porosity is about 0.15.     

Trabecular bone modeling and subcapital femoral fracture

Fragility fractures, including neck of femur fractures, result from reductions in the amount, quality and architecture of bone. The aim of this study was to compare the cancellous bone structure, and static indices of bone turnover, in female patients who had sustained fragility fracture at the femoral neck, with age-matched females without fragility fracture. Bone samples were taken from the intertrochanteric region of the proximal femur of female patients undergoing hip arthroplasty surgery for a subcapital fragility fracture of the femoral neck (#NOF) or from age-matched female control individuals at routine autopsy. The histomorphometric data, which were normally distributed, indicated no difference between the mean values for any of the structural parameters in control and fracture samples. In particular, the BV/TV values were not different and did not change significantly with age in these cohorts of individuals aged >65 years. The static indices of bone turnover, eroded surface (ES/BS) and osteoid surface (OS/BS), were positively correlated with age in the >65-year-old control group (p<0.05 and p<0.03, respectively). The median values for these indices were not different between the fracture and control groups. However, both the median and the range of OS/BS values were increased for >65-year-old controls compared with a group of younger females aged <65 years, suggesting an increase in bone formation in older females in the proximal femur after 65 years of age. When the data were further interrogated, a reduction in the percentage osteoid surface to eroded surface quotient (OS/ES) was found for the fracture group compared with the age-matched control group. These data indicate that perturbations in bone formation and/or resorption surface are potentially important in producing bone in the proximal femur with increased propensity to fracture. These data also support the concept that trabecular bone modeling may be a factor influencing bone strength in addition to bone mass.     

Relevance of osteoporosis in women with fracture of the femoral neck.

A prospective study of fractures of the femoral neck was conducted over 12 months in order to ascertain the relevance of generalised osteoporosis as determined by metacarpal morphometry. A series of some 200 women sustaining a fracture of the femoral neck after minor trauma had bone mass measurements similar to those of a control population of normal women, and 16% were not osteoporotic. A history of previous fractures was documented in one third of the women, but this was unrelated to the presence or severity of osteoporosis, although over half of the fractures had occurred within the previous four years. Trochanteric fractures were seen more commonly in severely osteoporotic women (p less than 0.005), whereas cervical fractures predominated in those who were not osteoporotic. These findings support the hypothesis that postural instability is the major determinant for femoral neck fracture and that generalised osteoporosis, rather than being a prerequisite for fracture, merely determines the type of fracture sustained.     

Work to fracture of canine femoral bone

The work-to-fracture of canine femoral bone has been measured using the technique of Tattersall and Tappin (1966). The work required to fracture a specimen in three point bending by slow crack propagation through a triangular cross section is obtained from the load-deformation curve. The area of the resulting fracture surface is measured by macrophotographic techniques, and the work-to-fracture is calculated as work per unit area. The values of fracture “toughness” measured in this way ranged from 5.36 × 10³ J/m² to 1.55 × 10⁴ J/m² in the samples tested with a mean of 9.03 × 10³ J/m² and a standard deviation of 3.27 × 10³ J/m². The work-to-fracture was found to vary with transverse variation in location in the femoral shaft. Scanning electron microscope photographs of the fracture surfaces indicate that the nature of the failure is similar to that of fiber reinforced composite materials. Samples which failed by catastrophic crack propagation were characterized by smooth fracture surfaces and had larger osteons than those which failed by slow crack propagation.     

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study

BackgroundBenzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg.Methods and findingsThe retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score–stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables.ConclusionsIn US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine–opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

In a retrospective cohort study, Dr. Wayne Ray and colleagues investigate concurrent opioid and hypnotic use and mortality in older adults in US.     

Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture.

OBJECTIVE--To evaluate the contribution of specific nutritional deficiencies (as indicated by zinc; vitamin A, C, and E; albumin; and haemoglobin concentrations) to the risk of pressure sores. DESIGN--Observational cohort study. SETTING--St James''s University Hospital, Leeds. SUBJECTS--21 elderly patients presenting consecutively to the orthopaedic unit with femoral neck fracture. MAIN OUTCOME MEASURE--Full thickness epidermal break over a pressure bearing surface. RESULTS--10 patients (48%) developed a pressure sore during their hospital stay. Indices of zinc status and concentrations of albumin, haemoglobin, and vitamins A and E were similar in patients who developed a pressure sore and those who did not. Mean leucocyte vitamin C concentration, however, was 6.3 (SD 2.2) micrograms/10(8) cells in patients who developed a pressure sore as compared with 12.8 (4.6) micrograms/10(8) cells in patients who did not. CONCLUSIONS--Low concentrations of leucocyte vitamin C appear to be associated with subsequent development of pressure sores in elderly patients with femoral neck fractures.     

Finite-element modelling of femoral shaft fracture fixation techniques post total hip arthroplasty.

The presence of a femoral prosthesis superior to a shaft fracture severely complicates fixation and treatment. This study uses two-dimensional, multithickness, plane stress finite-element models of a femur with prosthesis to investigate the stresses developed with the application of three popular fixation techniques: revision to a long stem prosthesis, lateral plating with a cortical bone allograft strut and cerclage wires, and custom plate application with proximal Parham band fixation with distal cortical screws (Ogden plate). The plate and bone contact as well as the fracture site contact were modelled by using orthotropic elements with custom-fit moduli so that only the normal stress to the interface was significant. A thermal analogy was used to model the cerclage and Parham band preloads so that representative preloads in the proximal fixation of the two types of plate treatments could be modelled. A parametric study was performed with the long-prosthesis model to show variations in stem lengths of one, two and three femoral diameters distal to the fracture site. The Ogden plate model showed a transfer of tensile stress near the proximal-most band, with the highest tensile stress being at the fracture site with evidence of stress shielding of the proximal lateral cortex. The cortical bone strut model showed a transfer of tensile stress to the bone strut but showed less shielding of the proximal cortex. The cerclage wires at the base of the bone strut showed the highest changes in load with the distalmost wire increasing to almost four times its original preload.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrinolytic capacity of arm and leg veins after femoral shaft fracture and acute myocardial infarction.

The local fibrinolytic activity generated in the leg and arm veins during venous occlusion (fibrinolytic capacity) and the systemic fibrinolytic activity were measured at intervals in 11 patients after fracture of the femoral shaft and in 11 patients after acute myocardial infarction. In both groups the fibrinolytic capacity of the leg veins and the systemic fibrinolytic activity were significantly reduced two days after the onset of tissue injury. The fibrinolytic capacity of the arm veins was not altered. These results provide a possible explanation for the predilection of venous thrombosis for the leg veins after accidental trauma and acute myocardial infarction.