4-Valent Human #Papillomavirus (4vHPV) #Vaccine in Preadolescents and Adolescents After 10 Years
http://pediatrics.aappublications.org/content/140/6/e20163947

For HPV types 6, 11, and 16, 89% to 96% of subjects remained seropositive through 10-years postvaccination. The preadolescents had 38% to 65% higher geometric mean titers at month 7, which remained 16% to 42% higher at 10 years compared with adolescents. No cases of HPV type 6, 11, 16, and 18–related diseases were observed. Ten subjects had a persistent infection of ≥6 months duration with vaccine-type HPV and 2 subjects had persistent infection for ≥12 months. No new serious adverse events were reported through 10 years.

CONCLUSIONS: A 3-dose regimen of the 4vHPV vaccine was immunogenic, clinically effective, and generally well tolerated in preadolescents and adolescents during 10 years of follow-up. These long-term findings support efforts to vaccinate this population against HPV before exposure

#Ketamine for Rapid Reduction of #Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial
https://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2017.17060647?journalCode=ajp

The reduction in SSI score at day 1 was 4.96 points greater for the ketamine group compared with the midazolam group (95% CI=2.33, 7.59; Cohen’s d=0.75). The proportion of responders (defined as having a reduction ≥50% in SSI score) at day 1 was 55% for the ketamine group and 30% for the midazolam group (odds ratio=2.85, 95% CI=1.14, 7.15; number needed to treat=4.0). Improvement in the Profile of Mood States depression subscale was greater at day 1 for the ketamine group compared with the midazolam group (estimate=7.65, 95% CI=1.36, 13.94), and this effect mediated 33.6% of ketamine’s effect on SSI score. Side effects were short-lived, and clinical improvement was maintained for up to 6 weeks with additional optimized standard pharmacotherapy in an uncontrolled follow-up.

Conclusions:
Adjunctive ketamine demonstrated a greater reduction in clinically significant suicidal ideation in depressed patients within 24 hours compared with midazolam, partially independently of antidepressant effect

#Treadmill Exercise on Motor Symptoms in Patients With De Novo #Parkinson Disease

https://jamanetwork.com/journals/jamaneurology/article-abstract/2664948?redirect=true

A total of 128 patients were included in the study (mean SD age, 64 9 years; age range, 40-80 years; 73 57.0% male; and 108 84.4% non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson’s Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, −1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe.

Conclusions and Relevance High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease

#Metaplastic Cells in the Stomach Arise, Independently of Stem Cells, via Dedifferentiation or Transdifferentiation of #Chief Cells
http://www.gastrojournal.org/article/S0016-5085(17)36690-8/pdf

Spasmolytic polypeptide-expressing metaplasia (SPEM) develops in patients with chronic atrophic gastritis due to infection with Helicobacter pylori; it might be a precursor to intestinal metaplasia and gastric adenocarcinoma. Lineage tracing experiments of the gastric corpus in mice have not established whether SPEM derives from proliferating stem cells or differentiated, post-mitotic zymogenic chief cells in the gland base. We investigated whether differentiated cells can give rise to SPEM using a non-genetic approach in mice. Mice were given intraperitoneal injections of 5-fluorouracil, which blocked gastric cell proliferation, plus tamoxifen to induce SPEM. Based on analyses of molecular and histological markers, we found SPEM developed even in the absence of cell proliferation. SPEM therefore did not arise from stem cells. In histologic analyses of gastric resection specimens from 10 patients with adenocarcinoma, we found normal zymogenic chief cells that were transitioning into SPEM cells only in gland bases, rather than the proliferative stem cell zone. Our findings indicate that SPEM can arise by direct reprogramming of existing cells—mainly of chief cells

#Screening in the community to reduce #fractures in older women (SCOOP): a randomised controlled trial
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)32640-5/fulltext

We did a two-arm randomised controlled trial in women aged 70–85 years to compare a screening programme using the Fracture Risk Assessment Tool (FRAX) with usual management

Treatment was recommended in 898 (14%) of 6233 women. Use of osteoporosis medication was higher at the end of year 1 in the screening group compared with controls (15% vs 4%), with uptake particularly high (78% at 6 months) in the screening high-risk subgroup. Screening did not reduce the primary outcome of incidence of all osteoporosis-related fractures (hazard ratio HR 0·94, 95% CI 0·85–1·03, p=0·178), nor the overall incidence of all clinical fractures (0·94, 0·86–1·03, p=0·183), but screening reduced the incidence of hip fractures (0·72, 0·59–0·89, p=0·002). There was no evidence of differences in mortality, anxiety levels, or quality of life.

Interpretation
Systematic, community-based screening programme of fracture risk in older women in the UK is feasible, and could be effective in reducing hip fractures

Manipulating #beliefs about losing control causes checking #behaviour
http://www.sciencedirect.com/science/article/pii/S221136491730115X

Cognitive theories of obsessive-compulsive disorder (OCD) posit that maladaptive beliefs lead to the development of symptoms. However, psychometric studies have provided mixed evidence regarding whether beliefs about control over thoughts predict OCD symptoms above and beyond other obsessive beliefs. Clinical reports have documented concerns among those diagnosed with OCD regarding a potential loss of control over their thoughts and behaviour, indicating that broadening the scope of beliefs about control by integrating aspects of losing control may better explain their role in OCD. In this study, 133 undergraduate participants underwent a bogus EEG session and received (positive or negative) false feedback about the possibility that they may lose control over their thoughts and behaviour, and completed a task asking them to control the pace of pictures. As hypothesized, participants in the high (versus low) beliefs about losing control condition checked significantly more often which keys they should use to control the pictures, t(106.95) = 2.28, p = .02, d = .44, demonstrating that manipulating beliefs about control can impact checking behaviour when a potential loss of control is emphasized. Also, checking behaviour predicted a lower desire for control, such that compulsions may be seen as opportunities to re-establish disrupted control cognitions.

#Atopic dermatitis and #psoriasis: two different immune diseases or one spectrum?
http://www.sciencedirect.com/science/article/pii/S0952791517301061

Highlights
•Psoriasis and AD are diseases of distinct T-cell ‘polar’ subsets.

•Targeting Th17/IL-17 is an extremely effective treatment for psoriasis.

•Targeting Th2/IL-4 & IL-13 is a highly effective treatment for atopic dermatitis.

•However, specific sub-types of atopic dermatitis blend Th17 and Th2 cytokine axes.

•Optimal treatment of AD across subtypes might require targeting multiple cytokines.

#Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic #stroke: a randomised controlled trial
http://svn.bmj.com/content/early/2017/11/08/svn-2017-000104

348 patients were enrolled: 179 in the GBE group and 169 in the control group. With 18 patients lost to follow-up, the dropout rate was 5.17%. Admission data between two groups were similar, but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores (−2.77±0.21 vs −1.99±0.23, P=0.0116 (30 days); −3.34±0.24 vs −2.48±0.26, P=0.0165 (90 days); −4.00±0.26 vs −2.71±0.26, P=0.0004 (180 days)) compared with controls. The National Institutes of Health Stroke Scale scores at 12 and 30 days, the modified Rankin Scale scores for independent rate at 30, 90 and 180 days, and the Barthel Index scores at 30, 90 and 180 days in the GBE group were significantly improved compared with controls. Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30, 90 and 180 days, Webster’s digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days. No significant differences were seen in the incidence of adverse events or vascular events.

Conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events

Effect of Different Doses of #Galcanezumab vs Placebo for Episodic #Migraine Prevention
https://jamanetwork.com/journals/jamaneurology/fullarticle/2665408

Of the 936 patients assessed, 410 met entry criteria (aged 18-65 years with 4-14 migraine headache days per month and migraine onset prior to age 50 years) and were randomized to receive placebo or galcanezumab.For the primary end point, galcanezumab, 120 mg, significantly reduced migraine headache days compared with placebo (99.6% posterior probability −4.8 days; 90% BCI, −5.4 to −4.2 days vs 95% superiority threshold Bayesian analysis −3.7 days; 90% BCI, −4.1 to −3.2 days). Adverse events reported by 5% or more of patients in at least 1 galcanezumab dose group and more frequently than placebo included injection-site pain, upper respiratory tract infection, nasopharyngitis, dysmenorrhea, and nausea.

Conclusions and Relevance Monthly subcutaneous injections of galcanezumab, both 120 mg and 300 mg, demonstrated efficacy (repeated-measures analysis) for the preventive treatment of migraine and support further development in larger phase 3 studies. All dosages were safe and well tolerated for the preventive treatment of episodic migraine

The long-term effects of faecal #microbiota transplantation for gastrointestinal symptoms and general health in patients with recurrent #Clostridium difficile infection
http://onlinelibrary.wiley.com/doi/10.1111/apt.14443/abstract

Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection. In short-term the treatment has been shown to be safe, however, there are no large, long-term follow-up studies looking into the potential adverse effects There was no difference in the incidence of severe diseases (inflammatory bowel disease, cancer, autoimmune disease, allergy, neurological diseases) between the patient groups. In addition, weight gain did not differ between treatment groups. The FMT treated patients reported that their bowel habits improved significantly faster, they had less irregular bowel function and less symptoms of upper GI-tract when compared to the patients treated with antibiotics. Significantly more patients in FMT-group reported that their mental health improved after the treatment. The willingness to receive FMT treatment for potential new C. difficile infection was significantly higher in both treatment groups compared to other treatment options.

Conclusion
Our study highlights that FMT is a durable, safe and acceptable treatment option for patients with recurrent C. difficile infection also in long term, and it shows potential benefits over antimicrobial treatment

Risk of posttransplant #hepatocellular carcinoma recurrence is greater in recipients with higher #platelet counts in living donor liver transplantation
http://onlinelibrary.wiley.com/doi/10.1002/lt.24961/abstract

Platelets interact with tumor cells and promote metastasis. The importance of platelets in posttransplant hepatocellular carcinoma (HCC) recurrence is unclear. Thus, we aimed to evaluate the association between preoperative platelet count (PLT) and HCC recurrence after living donor liver transplantation. Of 359 recipients of livers from living donors for HCC, 209 of 240 patients who had preoperative PLT ≤75 × 109/L were matched with 97 of 119 patients who had preoperative PLT >75 × 109/L using propensity score matching, with an unfixed matching ratio based on factors such as tumor biology. The cutoff value of 75 × 109/L was set based on optimum stratification analysis. Survival analysis was performed with death as a competing risk event. The primary outcome was overall HCC recurrence. The median follow-up time was 59 months. Before matching, recurrence probability at 1, 2, and 5 years after transplantation was 4.7%, 9.2%, and 11.3% for the low platelet group and 14.5%, 23.0%, and 30.5% for the high platelet group. Recurrence risk was significantly greater in the high platelet group in both univariate (hazard ratio HR = 3.09; 95% confidence interval CI, 1.86-5.14; P < 0.001) and multivariate analyses (HR = 2.10; 95% CI, 1.23-3.60; P =  0.007). In the matched analysis, recurrence risk was also greater in the high platelet group in both univariate (HR = 2.33; 95% CI, 1.36-4.01; P =  0.002) and multivariate analyses (HR = 1.90; 95% CI, 1.02-3.54; P =  0.04). Preoperative PLT had no interaction with the Milan criteria, alpha-fetoprotein level, Edmonson grade, microvascular invasion, or intrahepatic metastasis. Incorporation of preoperative PLT into the Milan criteria significantly improved predictive power. Inflammation-based scores including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the inflammation-based index did not show superiority to preoperative PLT in predicting HCC recurrence. In conclusion, preoperative PLT appears to be an important host factor affecting HCC recurrence after living donor liver transplantation

Trial of Contralateral Seventh Cervical #Nerve Transfer for #Spastic Arm Paralysis
http://www.nejm.org/doi/full/10.1056/NEJMoa1615208

Spastic limb paralysis due to injury to a cerebral hemisphere can cause long-term disability. We investigated the effect of grafting the contralateral C7 nerve from the nonparalyzed side to the paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury

The mean increase in Fugl–Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft.

CONCLUSIONS
In this single-center trial involving patients who had had unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand

Effectiveness of #ravidasvir plus #sofosbuvir in interferon-naïve and treated patients with chronic hepatitis #C genotype-4
http://www.journal-of-hepatology.eu/article/S0168-8278(17)32286-9/fulltext

•Ravidasvir is a new NS5A inhibitor for HCV.
•Sofosbuvir + Ravidasvir with or without RBV has achieved very high SVR rates.
•Results are comparable for both patients with and without cirrhosis.
•Serious adverse events were noticed in very few treated patients.

A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated.

Conclusions
Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments

#Erectile dysfunction in the trajectory of #cardiovascular disease
http://journals.sagepub.com/doi/full/10.1177/1358863X17744038 .

The study findings advance our knowledge regarding the connection between ED and vascular dysfunction. The association of ED with endothelial dysfunction and early atherosclerosis provides evidence that ED may serve as a marker of early vascular disease that is easily ascertained by clinical history taking. The connection may reflect shared underlying mechanisms leading to ED and CVD. Similar pathophysiology contributes to both endothelial dysfunction and ED, including loss of nitric oxide bioavailability and increased inflammatory activation

The present study emphasizes the relevance of ED to understanding the trajectory of CVD. A simple standardized ED screening may identify early vascular dysfunction. Similarly, vascular dysfunction may serve as a surrogate marker to evaluate the efficacy of cardiovascular targeted therapies in men with ED. The presence of ED portends a higher risk of future cardiovascular events, particularly in intermediate risk men, and may serve as an opportunity for intensification of cardiovascular risk prevention strategies.2 The findings add to the growing evidence supporting additional trials to determine the clinical impact of ED screening and the appropriate cardiovascular-directed evaluation and treatment of men with ED

Potential effect modifiers of the association between physical #activity patterns and #joint symptoms in middle aged women
http://onlinelibrary.wiley.com/doi/10.1002/acr.23430/abstract

To examine whether body mass index (BMI), menopausal status and hormone therapy (HT) use modify the association between physical activity (PA) patterns throughout middle age and incidence and prevalence of joint symptoms in later middle age in women

The groups representing ‘fluctuating’ (odds ratio [OR]=1.34, 99% confidence interval [CI]=1.04-1.72) and ‘none-or-low’ physical activity (OR=1.60, CI =1.08-2.35) had higher odds of incident joint symptoms than those ‘meeting guidelines-at-all-times’. Stratification by BMI showed that this association was statistically significant in the obese group only. No evidence was found for effect modification by menopausal status or HT use. The findings were similar for prevalent joint symptoms.

Conclusions
Maintaining at least low levels of physical activity throughout middle age was associated with lower prevalence and incidence of joint symptoms in later life. This apparent protective effect of physical activity on joint symptoms was stronger in obese women than in under or normal weight women, and not related to menopause and HT status