BACKGROUND: Significant advances have been made in the global effort to eradicate polio. Vaccine-associated poliovirus, or other enteroviruses, may still affect the anterior horn cell and cause acute flaccid paralysis. Following the acute disease, residual paralysis results in lower motor neuron weakness, altered growth and deformity. Our study aims to describe the clinical manifestations of a group of children that mimic that of classic paralytic poliomyelitisMETHODS: We identified six children from our paediatric orthopaedic database that presented with polio-like deformities. Their clinical and imaging records were reviewed and described, together with the clinical manifestations of paralytic poliomyelitisRESULTS: Limb hypoplasia, pathological gait patterns and foot deformities were consistent features. The median leg length discrepancy was 2.5 cm (range 2-4 cm). The gait patterns observed included a Trendelenburg gait in 33% (n=2), a short limb gait in 50% (n=3), and one case with a combination of Trendelenburg, short limb and steppage gait. Tensor fascia lata contracture was present in 50% (n=3) of our patients. Foot deformities ranged from calcaneo-cavo-valgus to equino-cavo-varus deformitiesCONCLUSION: Despite significant advances made in the global fight to eradicate polio, we still see children with clinical manifestations reminiscent of the disease. Orthopaedic surgeons should remain familiar with the assessment and diagnosis of the sequelae of paralytic poliomyelitisLevel of evidence: Level 5

ABSTRACT Introduction: To determine the impact of time from biopsy to surgery on outcomes following radical prostatectomy (RP) as the optimal interval between prostate biopsy and RP is unknown. Material and methods: We identified 7, 350 men who underwent RP at our institution between 1994 and 2012 and had a prostate biopsy within one year of surgery. Patients were grouped into five time intervals for analysis: ≤ 3 weeks, 4-6 weeks, 7-12 weeks, 12-26 weeks, and > 26 weeks. Oncologic outcomes were stratified by NCCN disease risk for comparison. The associations of time interval with clinicopathologic features and survival were evaluated using multivariate logistic and Cox regression analyses. Results: Median time from biopsy to surgery was 61 days (IQR 37, 84). Median follow-up after RP was 7.1 years (IQR 4.2, 11.7) while the overall perioperative complication rate was 19.7% (1,448/7,350). Adjusting for pre-operative variables, men waiting 12-26 weeks until RP had the highest likelihood of nerve sparing (OR: 1.45, p = 0.02) while those in the 4-6 week group had higher overall complications (OR: 1.33, p = 0.01). High risk men waiting more than 6 months had higher rates of biochemical recurrence (HR: 3.38, p = 0.05). Limitations include the retrospective design. Conclusions: Surgery in the 4-6 week time period after biopsy is associated with higher complications. There appears to be increased biochemical recurrence rates in delaying RP after biopsy, for men with both low and high risk disease.

ABSTRACT Objectives: Radical prostatectomy (RP) for locally advanced prostate cancer may reduce the risk of metastasis and cancer-specific death. Herein, we evaluated the outcomes for patients with pT4 disease treated with RP. Materials and methods: Among 19,800 men treated with RP at Mayo Clinic from 1987 to 2010, 87 were found to have pT4 tumors. Biochemical recurrence (BCR)-free survival, systemic progression (SP) free survival and overall survival (OS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards regression models were used to assess the association of clinic-pathological features with outcome. Results: Median follow-up was 9.8 years (IQR 3.6, 13.4). Of the 87 patients, 50 (57.5%) were diagnosed with BCR, 30 (34.5%) developed SP, and 38 (43.7%) died, with 11 (12.6%) dying of prostate cancer. Adjuvant androgen deprivation therapy was administered to 77 men, while 32 received adjuvant external beam radiation therapy. Ten-year BCR-free survival, SP-free survival, and OS was 37%, 64%, and 70% respectively. On multivariate analysis, the presence of positive lymph nodes was marginally significantly associated with patients' risk of BCR (HR: 1.94; p=0.05), while both positive lymph nodes (HR 2.96; p=0.02) and high pathologic Gleason score (HR 1.95; p=0.03) were associated with SP. Conclusions: Patients with pT4 disease may experience long-term survival following RP, and as such, when technically feasible, surgical resection should be considered in the multimodal treatment approach to these men.

BACKGROUND:Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.OBJECTIVE:To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments.METHODSSearch methods: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database.Selection criteria: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza.Data collection and analysis: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers.MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances.Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P < 0.0001). This represents a reduction in the time to first alleviation of symptoms from 7 to 6.3 days. There was no effect in asthmatic children, but in otherwise healthy children there was (reduction by a mean difference of 29 hours, 95% CI 12 to 47 hours, P = 0.001). Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days, P < 0.00001), equating to a reduction in the mean duration of symptoms from 6.6 to 6.0 days. The effect in children was not significant. In subgroup analysis we found no evidence of a difference in treatment effect for zanamivir on time to first alleviation of symptoms in adults in the influenza-infected and non-influenza-infected subgroups (P = 0.53).Hospitalisations. Treatment of adults with oseltamivir had no significant effect on hospitalisations: risk difference (RD) 0.15% (95% CI -0.78 to 0.91). There was also no significant effect in children or in prophylaxis. Zanamivir hospitalisation data were unreported.Serious influenza complications or those leading to study withdrawal.In adult treatment trials, oseltamivir did not significantly reduce those complications classified as serious or those which led to study withdrawal (RD 0.07%, 95% CI -0.78 to 0.44), nor in child treatment trials; neither did zanamivir in the treatment of adults or in prophylaxis. There were insufficient events to compare this outcome for oseltamivir in prophylaxis or zanamivir in the treatment of children.Pneumonia.Oseltamivir significantly reduced self reported, investigator-mediated, unverified pneumonia (RD 1.00%, 95% CI 0.22 to 1.49); number needed to treat to benefit (NNTB) = 100 (95% CI 67 to 451) in the treated population. The effect was not significant in the five trials that used a more detailed diagnostic form for pneumonia. There were no definitions of pneumonia (or other complications) in any trial. No oseltamivir treatment studies reported effects on radiologically confirmed pneumonia. There was no significant effect on unverified pneumonia in children. There was no significant effect of zanamivir on either self reported or radiologically confirmed pneumonia. In prophylaxis, zanamivir significantly reduced the risk of self reported, investigator-mediated, unverified pneumonia in adults (RD 0.32%, 95% CI 0.09 to 0.41); NNTB = 311 (95% CI 244 to 1086), but not oseltamivir.Bronchitis, sinusitis and otitis media.Zanamivir significantly reduced the risk of bronchitis in adult treatment trials (RD 1.80%, 95% CI 0.65 to 2.80); NNTB = 56 (36 to 155), but not oseltamivir. Neither NI significantly reduced the risk of otitis media and sinusitis in both adults and children.Harms of treatment.Oseltamivir in the treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90 to 7.39); number needed to treat to harm (NNTH) = 28 (95% CI 14 to 112) and vomiting (RD 4.56%, 95% CI 2.39 to 7.58); NNTH = 22 (14 to 42). The proportion of participants with four-fold increases in antibody titre was significantly lower in the treated group compared to the control group (RR 0.92, 95% CI 0.86 to 0.97, I2 statistic = 0%) (5% absolute difference between arms). Oseltamivir significantly decreased the risk of diarrhoea (RD 2.33%, 95% CI 0.14 to 3.81); NNTB = 43 (95% CI 27 to 709) and cardiac events (RD 0.68%, 95% CI 0.04 to 1.0); NNTB = 148 (101 to 2509) compared to placebo during the on-treatment period. There was a dose-response effect on psychiatric events in the two oseltamivir "pivotal" treatment trials, WV15670 and WV15671, at 150 mg (standard dose) and 300 mg daily (high dose) (P = 0.038). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75 to 10.29); NNTH = 19 (95% CI 10 to 57). There was a significantly lower proportion of children on oseltamivir with a four-fold increase in antibodies (RR 0.90, 95% CI 0.80 to 1.00, I2 = 0%).Prophylaxis.In prophylaxis trials, oseltamivir and zanamivir reduced the risk of symptomatic influenza in individuals (oseltamivir: RD 3.05% (95% CI 1.83 to 3.88); NNTB = 33 (26 to 55); zanamivir: RD 1.98% (95% CI 0.98 to 2.54); NNTB = 51 (40 to 103)) and in households (oseltamivir: RD 13.6% (95% CI 9.52 to 15.47); NNTB = 7 (6 to 11); zanamivir: RD 14.84% (95% CI 12.18 to 16.55); NNTB = 7 (7 to 9)). There was no significant effect on asymptomatic influenza (oseltamivir: RR 1.14 (95% CI 0.39 to 3.33); zanamivir: RR 0.97 (95% CI 0.76 to 1.24)). Non-influenza, influenza-like illness could not be assessed due to data not being fully reported. In oseltamivir prophylaxis studies, psychiatric adverse events were increased in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07 to 2.76); NNTH = 94 (95% CI 36 to 1538) in the study treatment population. Oseltamivir increased the risk of headaches whilst on treatment (RD 3.15%, 95% CI 0.88 to 5.78); NNTH = 32 (95% CI 18 to 115), renal events whilst on treatment (RD 0.67%, 95% CI -2.93 to 0.01); NNTH = 150 (NNTH 35 to NNTB > 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116).AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence.

The lomas formations of the Peruvian and Atacama deserts are characterized by both climatic and floristic spatial heterogeneity, as well as non-contiguous pockets of relatively distinct flora. We examined two distinct types of communities in Parque Nacional Pan de Azúcar in Chile, the low-elevation arroyo and bajada community, and the high-elevation fog-zone community. We determined the distribution with elevation of the dominant perennial plant species in a single arroyo community, as well as the distribution of associated climatic characteristics. Climatic conditions (including air temperature, relative humidity, and wind speed and direction) were recorded from June, 1999, to March, 2001, for the arroyo, as well as for a medium-elevation inland site with little vegetation, and a high-elevation fog-zone site with copious vegetation. The fog layer, or camanchaca, derived from the marine inversion layer ubiquitous to the Peruvian and Atacama deserts was found to be more persistent, though weaker, during the summer months and somewhat more condensed and shallower in the winter months, with uncharacteristically dry air and high temperatures occurring at and above 400 m elevation during the late fall and early winter of 2000. The reduction or increase in the maximum elevation of the camanchaca or a change in the rainfall regime of the park may have broad implications for the distribution or even presence of certain species in Parque Nacional Pan de Azúcar. Vegetation patterns appear to be strongly dependent on inversion layer development, and perhaps on its subsidence during the winter. A number of species prevalent at low-elevation sites may have little advantage at a high-elevation foggy site, whereas the consistently high humidity at low elevations would be a boon to any desert plant accustomed to low precipitation. If we are to successfully assess the effects of changes in southern Pacific weather patterns, it will become necessary to more closely examine the local variation in climate and plant distribution in these regions, on sets of species with known distributions and in environments whose climatic conditions are particularly well-characterized

Las "lomas", formaciones de los desiertos Peruano y de Atacama, se caracterizan por su heterogeneidad climática y florística, así como también por la discontinuidad de una vegetación relativamente distintiva y particular. Se investigaron dos grupos distintos de comunidades vegetales en el Parque Nacional Pan de Azúcar en Chile, las comunidades de baja elevación "arroyo" y "bajada", y la comunidad de la zona de niebla a mayor elevación. Se determinó la distribución altitudinal de las especies de plantas perennes dominantes en un arroyo, así como la distribución de las características climáticas asociadas. Las variables climáticas (incluyendo la temperatura ambiental, la humedad relativa, y la velocidad y dirección del aire) fueron registradas desde el mes de junio de 1999 hasta marzo de 2001, en el arroyo, así como en un sitio de elevación media en el interior del parque con poca vegetación y en otro sitio de alta elevación y vegetación abundante en la zona de niebla. El nivel de niebla, o camanchaca, derivada de la inversión marítima omnipresente en los desiertos Peruano y de Atacama, fue más persistente, aunque más débil, durante los meses de verano, y algo mas condensada y superficial durante los meses de invierno, con aire inusualmente seco y caliente sobre los 400 m durante el final del otoño e inicios del invierno de 2000. La reducción o el incremento en la elevación máxima de la camanchaca o un cambio en el régimen de precipitación podría tener grandes implicaciones en la distribución o aun más sobre la presencia de ciertas especies en el Parque. El patrón de distribución de las plantas parece ser fuertemente dependiente del desarrollo de la inversión marítima, y posiblemente de su descenso durante el invierno. Algunas especies comunes en sitios de baja elevación podrían tener poca ventaja en sitios altos y nublados, mientras que la alta humedad en los arroyos daría gran ventaja a cualquier planta desértica acostumbrada a la escasez de lluvias. Si quisiéramos discutir exitosamente los efectos de los cambios en los patrones climáticos del Pacifico Sur, sería necesario examinar cuidadosamente la variación climática local asociada a la distribución de la vegetación in estas regiones, considerando especies de distribución bien conocida y en ambientes cuyas condiciones climáticas estén particularmente bien caracterizadas