Collaborative overview of randomised trials of antiplatelet therapy--III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients. Antiplatelet Trialists' Collaboration.

OBJECTIVE--To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients. DESIGN--Overviews of all randomised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematically. SETTING--53 trials (total 8400 patients) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery; nine trials (600 patients) of antiplatelet therapy versus control in other types of immobility; 18 trials (1000 patients) of one antiplatelet regimen versus another. RESULTS--Overall, a few weeks of antiplatelet therapy produced a highly significant (2P < 0.00001) reduction in deep venous thrombosis. 25% of patients allocated antiplatelet therapy versus 34% of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography, representing prevention in about 90 patients per 1000 allocated antiplatelet therapy. There was an even greater proportional reduction in pulmonary embolism: such emboli were detected among 47 (1.0%) antiplatelet allocated patients versus an adjusted control total of 129 (2.7%), representing prevention among about 17 patients per 1000 treated (2P < 0.00001). In analyses confined to surgical trials, the proportional reductions were similar and separately significant for nonfatal pulmonary embolism (0.7% antiplatelet therapy v 1.8% control; 2P < 0.00001) and for deaths attributed to pulmonary embolism (0.2% v 0.9%; 2P = 0.0001). There was a slight but non-significant excess of deaths from other causes (1.0% v 0.7%), which made the difference in total mortality nonsignificant, though still favourable (1.2% v 1.5%). Information on adding antiplatelet therapy to heparin was limited but, at least for pulmonary embolism, suggested more protection from the combination than from heparin alone. The proportional reduction in the odds of suffering a deep venous thrombosis was roughly the same in patients having general surgery, traumatic orthopaedic surgery, and elective orthopaedic surgery (and in medical patients who were at increased risk of thromboembolism). For pulmonary embolism the numbers affected were smaller, but again the reductions were highly significant both in general surgery (16 (0.5%) v 58 (1.7%) pulmonary emboli; 2P < 0.0001) and in orthopaedic surgery (28 (2.7%) v 63 (6.1%) pulmonary emboli; 2P < 0.0002). CONCLUSION--It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism, and many surgeons and physicians do not use it routinely for thromboprophylaxis, even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism. These results indicate that antiplatelet therapy--either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis (such as subcutaneous heparin)--should be considered.     

Patterns of Bisphosphonates Utilization in Patients under Age 45 in a Large Cohort of Commercial Insurance Beneficiaries in the United States

Background

The effectiveness and safety of bisphosphonates treatment used in the young population have not been well studied. Despite insufficient data on effectiveness and safety of bisphosphonates in young patients, bisphosphonates are still considered in younger patients at high risk for osteoporosis or fracture. The objectives of this study were to identify bisphosphonate initiators aged 10–45 years and describe their clinical characteristics and to assess time trends of bisphosphonate use over the past decade in a large U.S. population-based cohort.

Methods

Using the medical and pharmacy claims data from a U.S. commercial insurance (2003–2012), patients aged 10–45 years without malignancy who initiated an oral or intravenous bisphosphonate after at least 1 year of insurance enrollment were selected. Baseline demographics, comorbidities, medications and health care utilization were assessed in the year prior to initiating a bisphosphonate. The trend of bisphosphonate use over time was examined.

Results

There were 9,082 bisphosphonate initiators (0.02% of the same age group in the population). The mean age was 38.1 years and 79.6% female. Osteoporosis was the most common diagnosis (41.2%). At baseline, 10.8% had a diagnosis of fracture and 29.0% had a bone mineral density measured. Of those who used glucocorticoids (39%) at baseline, the mean 1-year cumulative prednisone-equivalent dose was 2,669 milligrams. The use of bisphosphonates in the young population significantly decreased over the past decade (p<0.001).

Conclusions

Among young patients aged 10–45, the use of bisphosphonates was uncommon and significantly decreased over the past decade in the U.S. While most patients initiating bisphosphonates had a diagnosis of osteoporosis and fracture in the preceding year, some had no recorded claims with a diagnosis of fracture, osteoporosis, or long-term glucocorticoids use at baseline. Future research is needed to examine the effectiveness and safety of bisphosphonates in young patients at risk for osteoporosis.     

Influence of Cervical Muscle Fatigue on Musculo-Tendinous Stiffness of the Head-Neck Segment during Cervical Flexion

Aim

The aim of this study is to determine if the fatigue of cervical muscles has a significant influence on the head-neck segment musculo-tendinous stiffness.

Methods

Ten men (aged 21.2 ± 1.9 years) performed four quick-release trials of flexion at 30 and 50% MVC before and after the induction of muscular fatigue on cervical flexors. Electromyographic activity was recorded on the sternocleidomastoids (SCM) and spinal erectors (SE), bilaterally. Musculo-tendinous stiffness was calculated through the quick-release method adapted to the head-neck segment.

Results

We noticed a significant linear increase of the head-neck segment musculo-tendinous stiffness with the increase of exertion level both before (P < 0.0001) and after the fatigue procedure (P < 0.0001). However, this linear relationship was not different before and after the fatigue procedure. EMG analysis revealed a significant increase of the root mean square for the right SCM (P = 0.0002), the left SCM (P < 0.0001), the right SE (P < 0.0001), and the left SE (P < 0.0001) and a significant decrease of the median power frequency only for the right (P = 0.0006) and the left (P = 0.0003) SCM with muscular fatigue.

Discussion

We did not find significant changes in the head-neck segment musculo-tendinous stiffness with fatigue of cervical muscles. We found a significant increase in EMG activity in the SCM and the SE after the induction of fatigue of the SCM. Our findings suggest that with fatigue of cervical flexors, neck muscle activity is modulated in order to maintain the musculo-tendinous stiffness at a steady state.     

Serum CEACAM1 Level Is Associated with Diagnosis and Prognosis in Patients with Osteosarcoma

Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) is a trans-membrane multifunctional cell adhesion molecule associated with tumor cell proliferation, apoptosis, angiogenesis, invasion, and migration during tumor development. In the present study, we evaluated serum CEACAM1 level in osteosarcoma patients to explore its diagnostic and prognostic value for this particular malignancy. Sera from 113 patients with primary osteosarcoma, 98 patients with benign bone tumors and 126 healthy controls were obtained. Serum CEACAM1 level was measured with ELISA and correlation with clinicopathological characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses as well as Cox proportional hazard models were used to evaluate diagnostic and prognostic significance. The results revealed that serum CEACAM1 level was significantly higher in osteosarcoma patients compared to benign bone tumors and healthy controls (455.2 ± 179.9 vs 287.4 ± 103.2, 260.8 ± 109.7 pg/ml, respectively). Osteosarcoma patients with larger tumors, later-tumor stages, low tumor grades, and distant metastases had much higher CEACAM1 compared to those with smaller tumors, earlier tumor stages, high tumor grades and non-distant metastases (P < 0.05 for all). Multivariate logistic regression analysis confirmed that high serum CEACAM1 level was an independent risk factor for distant metastases (OR = 3.02, 95%CI 1.65–4.17). To distinguish osteosarcoma patients from those with benign bone tumor and healthy controls, ROC/AUC analysis indicated an AUC of 0.81 (sensitivity 0.61; specificity 0.89) and an AUC of 0.77 (sensitivity 0.57; specificity 0.92), respectively. Osteosarcoma patients with higher CEACAM1 had relatively lower survival compared to those with low CEACAM1 (P < 0.01), and multivariate analyses for overall survival revealed that high serum CEACAM1 level was an independent prognostic factor for osteosarcoma (HR = 1.56, 95%CI 1.23–3.28). The present study suggested that elevated serum CEACAM1 level might be a novel diagnostic and prognostic biomarker for osteosarcoma patients.     

Distribution Features of Skeletal Metastases: A Comparative Study between Pulmonary and Prostate Cancers

Bone scintigraphies are widely applied for detecting bone metastases. The aim of this study was to investigate distribution features of bone metastases in pulmonary and prostate cancers. Bone scintigraphies were performed in 460 patients with pulmonary cancer and 144 patients with prostate cancer. Patients were divided into three groups according to the total number of bone metastases: few bone metastases, moderate bone metastases, and extensive bone metastases. We compared the distribution of bone metastases in the two cancers, and analyzed the relationship between the distribution of metastatic lesions and their metastatic patterns. A total of 2279 and 2000 lesions of bone metastases were detected in 258 patients with pulmonary cancer and 102 patients with prostate cancer, respectively. In patients with few bone metastases, the distributions of metastatic lesions in the vertebrae (χ² = 16.0, P = 0.000) and thoracic bones (χ² = 20.7, P = 0.002) were significantly different between pulmonary and prostate cancers. In cases with moderate bone metastases, the distributions in the vertebrae (χ² = 6.6, P = 0.010), pelvis (χ² = 15.1 P = 0.000), and thoracic bones (χ² = 38.8, P = 0.000) were also significantly different between the two cancers. However, in patients with extensive bone metastases, the distributions were very similar. As the total number of bone metastases increased, their distribution in pulmonary cancer did not noticeably change, but the distribution in the vertebrae and thoracic bones of prostate cancer patients significantly changed. Accordingly, the distribution characteristics of bone metastases differed in pulmonary and prostate cancers, mainly in the early stages of metastasis.     

HIGH-INTENSITY EXERCISE TRAINING INDUCES MORPHOLOGICAL AND BIOCHEMICAL CHANGES IN SKELETAL MUSCLES

In the present study we investigated the effect of two different exercise protocols on fibre composition and metabolism of two specific muscles of mice: the quadriceps and the gastrocnemius. Mice were run daily on a motorized treadmill, at a velocity corresponding to 60% or 90% of the maximal running velocity. Blood lactate and body weight were measured during exercise training. We found that at the end of training the body weight significantly increased in high-intensity exercise mice compared to the control group (P=0.0268), whereas it decreased in low-intensity exercise mice compared to controls (P=0.30). In contrast, the food intake was greater in both trained mice compared to controls (P < 0.0001 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively). These effects were accompanied by a progressive reduction in blood lactate levels at the end of training in both the exercised mice compared with controls (P=0.03 and P < 0.0001 for low-intensity and high-intensity exercise mice, respectively); in particular, blood lactate levels after high-intensity exercise were significantly lower than those measured in low-intensity exercise mice (P=0.0044). Immunoblotting analysis demonstrated that high-intensity exercise training produced a significant increase in the expression of mitochondrial enzymes contained within gastrocnemius and quadriceps muscles. These changes were associated with an increase in the amount of slow fibres in both these muscles of high-intensity exercise mice, as revealed by the counts of slow fibres stained with specific antibodies (P < 0.0001 for the gastrocnemius; P=0.0002 for the quadriceps). Our results demonstrate that high-intensity exercise, in addition to metabolic changes consisting of a decrease in blood lactate and body weight, induces an increase in the mitochondrial enzymes and slow fibres in different skeletal muscles of mice, which indicates an exercise-induced increase in the aerobic metabolism.     

Shoe Sole Tread Designs and Outcomes of Slipping and Falling on Slippery Floor Surfaces

A gait experiment was conducted under two shoe sole and three floor conditions. The shoe soles and floors were characterized by the tread and groove designs on the surface. The coefficients of friction (COF) on the floor in the target area were measured. The subjects were required to walk on a walkway and stepping on a target area covered with glycerol. The motions of the feet of the subjects were captured. Gait parameters were calculated based on the motion data. Among the 240 trials, there were 37 no-slips, 81 microslips, 45 slides, and 77 slips. It was found that the condition with shoe sole and floor had both tread grooves perpendicular to the walking direction had the highest COF, the shortest slip distance, and the lowest percentages of slide and slip. The condition with shoe sole and floor had both tread grooves parallel to the walking direction had the lowest COF and the longest slip distance among all experimental conditions. The Pearson’s correlation coefficients between slip distance and slip velocity, time to foot flat, foot angle, and compensatory step length were 0.82 (p<0.0001), 0.33 (p<0.0001), −0.54 (p<0.0001), and −0.51 (p<0.0001), respectively.     

Randomised controlled trial for evaluation of fitness programme for patients with chronic low back pain.

OBJECTIVE--To evaluate a progressive fitness programme for patients with chronic low back pain. DESIGN--Single blind randomised controlled trial. Assessments were carried out before and after treatment by an observer blinded to the study and included a battery of validated measures. All patients were followed up by postal questionnaire six months after treatment. SETTING--Physiotherapy department of orthopaedic hospital. SUBJECTS--81 patients with chronic low back pain referred from orthopaedic consultants for physiotherapy. The patients were randomly allocated to a fitness programme or control group. INTERVENTION--Both groups were taught specific exercises to carry out at home and referred to a back-school for education in back care. Patients allocated to the fitness class attended eight exercise classes over four weeks in addition to the home programme and backschool. RESULTS--Significant differences between the groups were shown in the changes before and after treatment in scores on the Oswestry low back pain disability index (P < 0.005), pain reports (sensory P < 0.05 and affective P < 0.005), self efficacy reports (P < 0.05), and walking distance (P < 0.005). No significant differences between the groups were found by the general health questionnaire or questionnaire on pain locus of control. A benefit of about 6 percentage points on the disability index was maintained by patients in the fitness group at six months. CONCLUSION--There is a role for supervised fitness programmes in the management of moderately disabled patients with chronic low back pain. Further clinical trials, however, need to be established in other centres to confirm these findings.     

The Association of Normal Range Glycated Hemoglobin with Restrictive Lung Pattern in the General Population

Glycated hemoglobin (HbA1c) is an important diagnostic indicator of diabetes mellitus, and some authors have argued that it is related to impaired lung function in the diabetic population. However, there was rare study for association between lung function and HbA1c in the non-diabetic population. We investigated whether HbA1c below the diagnostic threshold is related to deficits in lung function. We analyzed biochemical and spirometry data from a nation-wide, population-based, case-control study (the KNHANES IV and V). Eligible as cases were all native Koreans aged 40 years or more with no medical illness. A total of 3670 participants were divided into 4 groups according to HbA1c (%) as follows: Group I (n = 842), ≥ 4.0 and ≤ 5.3; Group II (n = 833), > 5.3 and ≤ 5.5; Group III (n = 898), > 5.5 and ≤ 5.7; and Group IV (n = 1097), > 5.7 and ≤ 6.4. Group I had the greatest forced vital capacity (FVC, 96.3 ± 0.5% pred, P < 0.0001), forced expiratory volume per second (FEV₁, 93.8 ± 0.5% pred, P < 0.0001) and FEV₁/FVC (0.792 ± 0.003, P < 0.0001) compared with the other groups. Linear regression showed that HbA1c was closely related to FVC (β = -6.972154, P < 0.0001) and FEV₁ (β = -5.591589, P < 0.0001), but not to FEV₁/FVC. Logistic regression analysis revealed a significant association between HbA1c and a restrictive spirometric pattern (FVC < 80% pred., FEV₁/FVC ≥ 0.70; OR = 3.772, 95% CI = 1.234-11.53), indicating that elevated HbA1c is closely associated with lung impairment in the non-diabetic population. In the healthy population, relatively high HbA1c level is associated with decrements of FVC and FEV₁ and may be a reliable predictor of poor lung function, especially the restrictive pattern.     

The role of adjuvant clodronate therapy for prevention of bone metastasis in breast cancer

Bisphosphonates are effective against increased bone resorption because they inhibit osteoclast activity. The use of these drugs is well established for the treatment of metastatic breast and other cancers; they reduce skeletal complications, hypercalcemia, bone pain, and metastatic progression and they can improve the overall survival and quality of life. Preclinical observations and early clinical data indicate that early bisphosphonate treatment reduces the incidence and the extent of newly developed metastases in breast cancer. There is considerable interest in determining whether bisphosphonate treatment is to prevent the incidence of bone metastases and associated complications. To date three randomized, controlled clinical trials have examined the effect of long-term use of clodronate (1600 mg/d po.) on the incidence of bone metastases, other metastases, the survival of patients, and the side effects of the study drug as well. All the trials have observed significant reduction of the occurrence of bone metastases, although this reduction was significant only during the medication period. One of the trials mentioned have shown an unexpected reduction in non-osseous metastases, and two of them have revealed significant improvements in the death rates. These promising results need further evaluation by large clinical trials with longer treatment periods to establish the clinical role of adjuvant bisphosphonate treatment of primary breast cancer.     

Postal questionnaire study of disability in the community associated with psoriasis.

OBJECTIVE: To study the disability caused by psoriasis in patients recorded as having psoriasis by their general practitioner. DESIGN: Postal questionnaire survey using the psoriasis disability index and SF-36. SETTING: Five general practices in Cleveland. SUBJECTS: Of 767 patients identified, 546 completed the questionnaire and 435 were eligible and gave informed consent. MAIN OUTCOME MEASURES: Scores on SF-36 and psoriasis disability index. RESULTS: The psoriasis disability index score was highly negatively correlated with all eight of the SF-36 health measures (P < 0.0001 for each), and the manual social classes scored higher than the non-manual social classes (P < 0.0001). The manual social class group scored significantly lower scores than the controls on all the SF-36 scales, and the non-manual group scored significantly lower for physical and mental role limitation (P < 0.0004 and P = 0.026), mental health (P < 0.0001), energy and vitality (P < 0.0004), and health perception (P < 0.0001). Also, the manual group had poorer health perception on five of the SF-36 variables when compared with the non-manual group. CONCLUSIONS: Patients with psoriasis have an overall lower perception of their quality of life than healthy controls, and those in the lower social classes suffer a greater degree of disability from their disease than the higher social classes.     

Regional versus General Anesthesia for Percutaneous Nephrolithotomy: A Meta-Analysis

ObjectiveTo compare the effectiveness and safety of regional anesthesia (RA) and general anesthesia (GA) for percutaneous nephrolithotomy (PNL).ResultsEight randomized controlled trials (RCTs) and six non-randomized controlled trials (nRCTs) involving 2270 patients were included. Patients receiving RA were associated with shorter operative time (−6.22 min; 95%CI, −9.70 to −2.75; p = 0.0005), lower visual analgesic score on the first and third postoperative day (WMD, −2.62; 95%CI, −3.04 to −2.19; p < 0.00001 WMD, −0.38; 95%CI, −0.58 to −0.18; p = 0.0002), less analgesic requirements (WMD, −59.40 mg; 95%CI, −78.39 to −40.40; p<0.00001), shorter hospitalization (WMD, −0.36d; 95%CI, −0.66 to −0.05; p = 0.02), less blood transfusion (RR, 0.61; 95%CI, 0.41 to 0.93; p = 0.02), fewer modified Clavion-Dindo Grade II (RR, 0.56; 95%CI, 0.37 to 0.83; p = 0.005), Grade III or above postoperative complications (RR, 0.51; 95%CI, 0.33 to 0.77; p = 0.001), and potential benefits of less fever (RR, 0.79; 95%CI, 0.61 to 1.02; p = 0.07), nausea or vomiting (RR, 0.54; 95%CI, 0.20 to 1.46; p = 0.23), whereas more intraoperative hypotension (RR, 3.13; 95%CI, 1.76 to 5.59; p = 0.0001) when compared with patients receiving GA. When nRCTs were excluded, most of the results were stable but the significant differences were no longer detectable in blood transfusion, Grade II and more severe complications. No significant difference in the total postoperative complications and stone-free rate were found.ConclusionsCurrent evidence suggests that both RA and GA can provide safe and effective anesthesia for PNL in carefully evaluated and selected patients. Each anesthesia technique has its own advantages but some aspects still remain unclear and need to be explored in future studies.     

Effect of advertising on awareness of symptoms of diabetes among the general public: the British Diabetic Association Study.

OBJECTIVE--To determine the impact of posters advertising symptoms of diabetes on public knowledge of these symptoms. DESIGN--Structured street interviews of members of the general public before, at the end of, and 10 weeks after a campaign advertising the main symptoms of diabetes. SETTING--Basingstoke and Wolverhampton. SUBJECTS--Three samples of 1000 members of the general public were interviewed. Samples were selected randomly but stratified to match the local population''s age (20-75), sex, social class, and racial characteristics. MAIN OUTCOME MEASURES--Knowledge of symptoms of diabetes; perceived seriousness of diabetes; and induction of anxiety about symptoms in the target population. RESULTS--Advertising significantly raised knowledge (without prompting) of symptoms: thirst, 245 before v 411 at end of campaign (P < 0.0001) v 341 after (P = 0.0012 v before); polyuria, 72 v 101 (P = 0.0211) v 92 (P = 0.5169); lethargy, 180 v 373 (P < 0.0001) v 298 (P < 0.0001); knowledge of weight loss and visual disturbance was unaffected. The number of subjects lacking knowledge of any symptoms was reduced from 550 to 388 (P < 0.0001). The perceived seriousness of diabetes was unaffected (mean 7.6 in each phase on a scale of 1 (not) to 10 (very). Before advertising, 449 (45%) claimed to have one or more symptoms of diabetes, but this number fell at the end of the campaign (403; P = 0.0419) and 10 weeks afterwards (278; P < 0.0001). CONCLUSIONS--An advertising campaign raised public knowledge of diabetes symptoms without inducing fear of diabetes or anxiety about symptoms. Its potential for achieving earlier detection of non-insulin dependent diabetes should be evaluated.     

Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study

Background

Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia.

Methods

In 1979 healthy behaviours were recorded on 2,235 men aged 45–59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined.

Findings

Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005).After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia.The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009.

Interpretation

A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low.     

Effects on birth weight and perinatal mortality of maternal dietary supplements in rural Gambia: 5 year randomised controlled trial .

OBJECTIVE: To test the efficacy in terms of birth weight and infant survival of a diet supplement programme in pregnant African women through a primary healthcare system. DESIGN: 5 year controlled trial of all pregnant women in 28 villages randomised to daily supplementation with high energy groundnut biscuits (4.3 MJ/day) for about 20 weeks before delivery (intervention) or after delivery (control). SETTING: Rural Gambia. SUBJECTS: Chronically undernourished women (twin bearers excluded), yielding 2047 singleton live births and 35 stillbirths. MAIN OUTCOME MEASURES: Birth weight; prevalence of low birth weight (< 2500 g); head circumference; birth length; gestational age; prevalence of stillbirths; neonatal and postneonatal mortality. RESULTS: Supplementation increased weight gain in pregnancy and significantly increased birth weight, particularly during the nutritionally debilitating hungry season (June to October). Weight gain increased by 201 g (P < 0.001) in the hungry season, by 94 g (P < 0.01) in the harvest season (November to May), and by 136 g (P < 0.001) over the whole year. The odds ratio for low birthweight babies in supplemented women was 0.61 (95% confidence interval 0.47 to 0.79, P < 0.001). Head circumference was significantly increased (P < 0.01), but by only 3.1 mm. Birth length and duration of gestation were not affected. Supplementation significantly reduced perinatal mortality: the odds ratio was 0.47 (0.23 to 0.99, P < 0.05) for stillbirths and 0.54 (0.35 to 0.85, P < 0.01) for all deaths in first week of life. Mortality after 7 days was unaffected. CONCLUSION: Prenatal dietary supplementation reduced retardation in intrauterine growth when effectively targeted at genuinely at-risk mothers. This was associated with a substantial reduction in the prevalence of stillbirths and in early neonatal mortality. The intervention can be successfully delivered through a primary healthcare system.     

Ingredient selection for plastic composite supports for L-(+)-lactic acid biofilm fermentation by Lactobacillus casei subsp. rhamnosus.

Plastic composite supports containing 50% agricultural products (oat hulls, soybean hulls, yeast extract, soybean flour, dried bovine erythrocytes, bovine albumin, and/or mineral salts) and 50% (wt/wt) polypropylene were produced by high-temperature twin-screw extrusion. The research employed two half sets of a five-factorial fractional design (2(5 - 1)) to evaluate the effects of different agricultural components on the properties of the plastic composite supports and to select the best plastic composite support formulation for lactic acid fermentation. The biofilm population was affected by the contact angle and relative hydrophobicity of the supports (r = 0.79 to 0.82). Lactic acid was produced by the suspended cells (r = 0.96) and the biofilm on the plastic composite support discs (r = 0.85). Incorporation of yeast extract into plastic composite supports enhanced growth of free and attached cells in minimal medium (P < 0.0001). The presence of soybean hulls, yeast extract, or mineral salts in plastic composite supports produced less hydrophobic supports (P < 0.0001) and enhanced cell attachment (P < 0.03). Under all conditions, suspended-cell and polypropylene disc controls gave negligible lactic acid production and cell density. Plastic composite supports containing soybean hulls, yeast extract, soybean flour, bovine albumin, and mineral salts gave the highest biofilm population (2.3 x 10(9) CFU/g of support), cell density (absorbance of 1.8 at 620 nm), and lactic acid concentration (7.6 g/liter) in minimal medium.     

Next generation sequencing demonstrates association between tumor suppressor gene aberrations and poor outcome in patients with cancer

Next generation sequencing is transforming patient care by allowing physicians to customize and match treatment to their patients’ tumor alterations. Our goal was to study the association between key molecular alterations and outcome parameters. We evaluated the characteristics and outcomes (overall survival (OS), time to metastasis/recurrence, and best progression-free survival (PFS)) of 392 patients for whom next generation sequencing (182 or 236 genes) had been performed. The Kaplan-Meier method and Cox regression models were used for our analysis, and results were subjected to internal validation using a resampling method (bootstrap analysis). In a multivariable analysis (Cox regression model), the parameters that were statistically associated with a poorer overall survival were the presence of metastases at diagnosis (P = 0.014), gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDKN2A alterations (P = 0.0001). The variables associated with a shorter time to metastases/recurrence were gastrointestinal histology (P = 0.004), APC (P = 0.008), PTEN (P = 0.026) and TP53 (P = 0.044) alterations. TP53 (P = 0.003) and PTEN (P = 0.034) alterations were independent predictors of a shorter best PFS. A personalized treatment approach (matching the molecular aberration with a cognate targeted drug) also correlated with a longer best PFS (P = 0.046). Our study demonstrated that, across diverse cancers, anomalies in specific tumor suppressor genes (PTEN, CDKN2A, APC, and/or TP53) were independently associated with a worse outcome, as reflected by time to metastases/recurrence, best PFS on treatment, and/or overall survival. These observations suggest that molecular diagnostic tests may provide important prognostic information in patients with cancer.     

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy

There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3^rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.