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Background: The European Centres for Disease Prevention and Control (ECDC) estimates that seasonal influenzacauses 4-50 million symptomatic infections in the EU/EEA each year and 15,000-70,000 European citizens die of causes associated with influenza. We used modelling methods to estimate influenza-associated mortality for the European Union by age group and country., Methods: We compiled influenza-associated respiratory mortality estimates for 31 countries around the world (11 countries in the EU) during 2002-2011 (excluding the 2009 pandemic). From these we extrapolated the influenza mortality burden for all 193 countries of the world, including the 28 countries of the EU, using a multiple imputation approach. To study the effect of vaccination programs, we obtained data from the EU-funded VENICE project regarding the percentage of persons over 65 who were vaccinated in each country; the data ranged from 2% to 82% between the 21 countries which provided estimates for the 2006/07 reference season., Results: We estimated that an average of 27,600 (range 16,200-39,000) respiratory deaths were associated with seasonal influenza in the 28 EU countries per winter; 88% were among people 65 years and older, and the rates of mortality in this age group were roughly 35 times higher compared with those < 65 years. Estimates varied considerably across the EU; for example, rates in the elderly ranged from 21.6 (12.5-35.1) per 100,000 in Portugal to 36.5 (16.4-62.5) in Luxembourg, a difference of nearly 70%. We were unable to find a negative correlation between vaccination coverage rates and influenza-associated mortality estimates in the elderly., Conclusion: Our EU estimate of influenza-associated respiratory mortality is broadly consistent with the ECDC estimate. More research is needed to explain the observed variation in mortality across the EU, and on possible bias that could explain the unexpected lack of mortality benefits associated with European elderly influenza vaccination programs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Ltd.)

Because the real-world impact of new vaccines cannot be known before they are implemented in national programs, post-implementation studies at the population level are critical. Studies based on analysis of hospitalization rates of vaccine-preventable outcomes are typically used for this purpose. However, estimates of vaccine impact based on hospitalization data are particularly prone to confounding, as hospitalization rates are tightly linked to changes in the quality, access and use of the healthcare system, which often occur simultaneously with introduction of new vaccines. Here we illustrate how changes in healthcare delivery coincident with vaccine introduction can influence estimates of vaccine impact, using as an example reductions in infant pneumonia hospitalizations after introduction of the 10-valent pneumococcal conjugate vaccine (PCV10) in Brazil. To this end, we explore the effect of changes in several metrics of quality and access to public healthcare on trends in hospitalization rates before (2008-09) and after (2011-12) PCV10 introduction in 2010. Changes in infant pneumonia hospitalization rates following vaccine introduction were significantly associated with concomitant changes in hospital capacity and the fraction of the population using public hospitals. Importantly, reduction of pneumonia hospitalization rates after PCV10 were also associated with the expansion of outpatient services in several Brazilian states, falling more sharply where primary care coverage and the number of health units offering basic and emergency care increased more. We show that adjustments for unrelated (non-vaccine) trends commonly employed by impact studies, such as use of single control outcomes, are not always sufficient for accurate impact assessment. We discuss several ways to identify and overcome such biases, including sensitivity analyses using different denominators to calculate hospitalizations rates and methods that track changes in the outpatient setting. Employing these practices can improve the accuracy of vaccine impact estimates, particularly in evolving healthcare settings typical of low- and middle-income countries., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Influenza vaccination control strategies in most countries rely on vaccination of seniors and other high risk groups. Although placebo-controlled randomized trials show influenza vaccine is effective in younger age groups, few seniors >70 years were studied even though they suffer >90% of influenza-related deaths. Excess mortality studies could not confirm a national decline in influenza-related mortality while vaccine coverage quadrupled. Cohort studies have consistently reported that vaccination reduces all-cause winter mortality by approximately 50%, an astonishing claim given only approximately 5% of all winter deaths are attributable to influenza. This VE overestimation has now been attributed to profound confounding frailty selection bias. A way forward includes a new generation of unbiased studies with laboratory endpoints, and requires an agreement that the evidence base was flawed. The latter may clear the way for more immunogenic vaccines for seniors and exploration of other influenza control strategies.

Influenza vaccination policy in most high-income countries attempts to reduce the mortality burden of influenza by targeting people aged at least 65 years for vaccination. However, the effectiveness of this strategy is under debate. Although placebo-controlled randomised trials show influenza vaccine is effective in younger adults, few trials have included elderly people, and especially those aged at least 70 years, the age-group that accounts for three-quarters of all influenza-related deaths. Recent excess mortality studies were unable to confirm a decline in influenza-related mortality since 1980, even as vaccination coverage increased from 15% to 65%. Paradoxically, whereas those studies attribute about 5% of all winter deaths to influenza, many cohort studies report a 50% reduction in the total risk of death in winter--a benefit ten times greater than the estimated influenza mortality burden. New studies, however, have shown substantial unadjusted selection bias in previous cohort studies. We propose an analytical framework for detecting such residual bias. We conclude that frailty selection bias and use of non-specific endpoints such as all-cause mortality have led cohort studies to greatly exaggerate vaccine benefits. The remaining evidence base is currently insufficient to indicate the magnitude of the mortality benefit, if any, that elderly people derive from the vaccination programme.

The design and synthesis of a series of analogues of sialyl Lewis(x)(1) which incorporate conformationally rigid tetralin and naphthalene ring systems(2-4) has led to novel compounds which have similar potency to 1 as inhibitors of cell adhesion.

Purpose: To report unilateral pupil-sparing third nerve palsy after use of sildenafil citrate (Viagra)., Method: Case report., Results: A 56-year-old man with a history of tobacco abuse was treated for erectile dysfunction. Viagra, 50 mg, was taken once without adverse effect. Three weeks later, the patient took a second dose of Viagra (50 mg); 36 hours later he experienced a complete pupil-sparing third nerve palsy. Erythrocyte sedimentation rate, blood glucose level, magnetic resonance imaging, and magnetic resonance angiography were normal., Conclusion: In a patient with microvascular disease, use of sildenafil may be associated with pupil-sparing third nerve palsy.

Objectives: Color Doppler ultrasound (CDU) diagnostic criteria for varicoceles are poorly defined, and the role of CDU in diagnosing varicoceles is controversial. The purpose of this study is to assess the diagnostic accuracy of CDU for varicoceles compared to physical examination., Methods: We prospectively studied 64 patients with CDU and collected the following data: maximum diameter of scrotal veins, the presence of a venous plexus, sum of the diameter of up to six veins of the plexus, and the duration and amplitude of flow change on Valsalva maneuver. To avoid interphysician variation, all patients were examined by one designated senior urologist with the sonographer remaining unaware of the findings., Results: CDU parameters of 127 testis units in 64 patients were analyzed and compared to the physical findings. Fifty-nine testis units were positive and 57 units were negative for varicocele on physical examination. In 11 testis units, results of physical examination were inconclusive regarding the presence of varicocele. The commonly accepted CDU criterion for varicocele (maximal vein diameter of 3 mm or greater) had a sensitivity of 53% and specificity of 91% compared to physical examination. We developed a new scoring system incorporating the maximal venous diameter (score 0 to 3), the presence of a venous plexus and the sum of the diameters of veins in the plexus (score 0 to 3), and the change of flow on Valsalva maneuver (score 0 to 3). Using a total score of 4 or more to define the presence of CDU-positive varicocele, we observed a sensitivity of 93% and a specificity of 85% when compared to physical examination. All moderate to large varicoceles found on physical examination were positive by CDU diagnosis using the scoring system, but the same group had only a 68% positive rate by traditional CDU diagnostic criteria., Conclusions: Using the proposed new scoring system, CDU has been shown to be a reliable and accurate method of diagnosis for varicoceles compared to the current reference standard physical examination. CDU has the advantages of being able to objectively examine venous plexus and measure blood flow parameters and to be less observer-dependent than physical examination.

Objectives: To evaluate the long-term result of prostatic stent treatment for patients with benign prostatic hyperplasia (BPH)., Methods: We reviewed our experience with prostatic stents in 24 patients with bladder outlet obstruction caused by BPH for whom up to 63 months of follow-up data were available., Results: Prostatic stents were successfully placed in 24 of 25 patients enrolled in the study. All 9 patients treated for urinary retention voided spontaneously after stent placement. In 14 (93%) of 15 patients with nonretention, voiding symptoms decreased by 50% or more. The stent was removed in 9 patients for persistence of symptoms, symptom recurrence, or stent migration. Nine patients died of unrelated causes during the follow-up period. The stents functioned adequately in these patients until death. In the remaining 6 patients, the stent was still in place at the last follow-up visit (range 12 to 52 months, average 35) after placement, and their Madsen-Iversen symptom scores ranged from 3 to 10. Fourteen patients underwent cystoscopy 1 to 37 months after stent placement. Epithelium did not completely cover the stent in any of these patients; however, no stone formation was noted., Conclusions: Prostatic stents can be effective in relieving bladder outlet obstruction caused by BPH. They appear to be most useful in patients at high surgical risk and with a limited life expectancy. However, stent removal, which can be difficult, may be required in more than one-third of patients. We recommend prostatic stent placement primarily in patients who would otherwise be relegated to an indwelling catheter.

We report our experience with successful treatment of 2 cases of severe recurrent vesicourethral anastomotic stricture after radical prostatectomy with endourethroplasty. Both patients had multiple failures of conventional treatments but have been free of stricture recurrence after endourethroplasty with 11 and 25 months follow-up, respectively. Follow-up urethroscopy showed open anastomotic segments with epithelialization after endourethroplasty in both patients. The patient who was continent prior to endourethroplasty remained continent afterward.

Objectives: To study the role of urethral sonography and color Doppler imaging in the evaluation of patients with urethral strictures and associated abnormalities., Methods: We reviewed our experience with 41 urethral sonographic studies in 35 patients and compared them to 33 retrograde urethrograms. For 6 recent cases, we also used color Doppler imaging to assess spongiosal tissue blood flow and the location of urethral arteries., Results: Both retrograde urethrography and urethral sonography assessed the caliber and length of the strictures well. Urethral sonography provided additional information about stricture involvement of the spongiosum, location of urethral arteries, and associated abnormalities (that is, periurethral abscess and urethrocutaneous fistula). This information was useful for the clinical stratification of urethral stricture disease and the planning of treatment., Conclusions: With the advantages of avoiding radiation to testis, providing real-time evaluation of the distensibility of the urethra, and having the capacity of assessing spongiosum and periurethral tissue involvement and urethral artery location, urethral sonography appears to offer more than retrograde urethrography for the evaluation of anterior urethral stricture.

We compared the current dollar inclusive costs of the two most commonly implanted penile prostheses with our pharmacologic erection program (PEP). The inclusive cost of implantation for the inflatable penile prosthesis (IPP) is $9,000 and for the malleable penile prosthesis (MPP) $3,150. The inclusive cost of PEP at maximal dose and maximal frequency of use over a five-year period is $3,450. Penile prosthesis was found to be more cost-effective for the long-term treatment of younger impotent men, whereas in the elderly group the use of PEP over a limited time span may be equally or more cost-effective.

Acquired renal cystic disease (ARCD) was initially reported to occur exclusively with patients on chronic hemodialysis for end-stage renal disease. To date, no cases of ARCD have been well documented in patients with end-stage renal disease treated solely by peritoneal dialysis. We report the occurrence of ARCD with renal cell carcinoma and hemorrhagic cyst formation in 2 patients with end-stage renal disease treated only with chronic ambulatory peritoneal dialysis for three and one-half and three years, respectively, since the onset of their renal failure. Both patients were found to have ARCD and complex masses on follow-up ultrasound examination after previous normal examinations. The findings were confirmed by computerized tomography (CT) scan and both patients underwent radical nephrectomy.

We have reviewed our experience with 10 patients who had leukemia and prostatic obstruction. Most of these patients had chronic lymphocytic leukemia, and all were stable. Following routine preoperative evaluation all underwent transurethral resection of the prostate (TURP). Two patients (20 per cent) had leukemic infiltration of the prostate. Our series confirms that TURP does not present undue risk to the patient with leukemia if the disease is stable and preoperative evaluation normal.

[3H]Spiperone binding to D2 dopamine receptors on bovine anterior pituitary membranes is of high affinity, saturable and unaffected by guanine nucleotides. Antagonist displacement of [3H]spiperone binding is characterised by pseudo Hill coefficients close to one and is unaffected by guanine nucleotides. Agonist displacements show pseudo Hill coefficients less than one and agonist affinities are reduced by guanine nucleotides, although pseudo Hill coefficients are essentially unchanged. Agonist displacement curves may be treated in terms of two agonist binding sites with different agonist affinities, and in the presence of guanine nucleotides the two-binding site model remains the best description of the data.

Unilateral injection of kainic acid (2.5-25 nmol) into rat anterior caudate putamen induced dose-related circling behaviour. Kainic acid (10 nmol) consistently caused initial weak ipsiversive circling lasting 1 h followed by prolonged strong contraversive rotation lasting in excess of 10 h. Unilateral intrastriatal administration of L-glutamic acid, or of monosodium L-glutamate, to normal rats, or administration of monosodium L-glutamate to rats with extensive decortication, did not induce circling behaviour. The simultaneous unilateral injection of monosodium L-glutamate (1 mumol) with kainic acid (10 nmol) did not modify circling behaviour induced by kainic acid. However, extensive decortication greatly reduced circling induced by unilateral intrastriatal kainic acid (10 nmol), and effect not reversed by the simultaneous administration of monosodium L-glutamate (1 mumol). Unilateral 6-hydroxydopamine lesions of the left nigrostriatal pathway abolished the initial ipsiversive rotation and potentiated the subsequent contraversive rotation for up to 4 h after intrastriatal injection of kainic acid (10 nmol). Peripheral administration of haloperidol (1 mg/kg i.p.) also abolished initial ipsiversive rotation and decreased the subsequent contraversive rotation. Electro-coagulation of the ipsilateral strio-nigral pathway prolonged the initial ipsiversive rotation produced by kainic acid, but markedly attenuated contraversive rotation. These findings suggest that circling induced by intrastriatal administration of kainic acid depends on intact corticostriate pathways, but it cannot be reproduced or modified by intrastriatal administration of glutamate. Kainic acid circling appears to be mediated via strio-nigral pathways, and to be modulated by dopaminergic function.

Modification of the en bloc resection of kidneys for cadaveric kidney transplant patient is described. A median sternotomy and division of the portal triad provide excellent exposure of the upper aorta above the celiac axis. This approach has been used in 40 cadaveric donors with no complications.

Retrograde pyelography to demonstrate the renal pelvis and ureters is a common urologic procedure. Newer contrast materials and better radiographic techniques have obviated many of the previous indications for retrograde studies were independently reviewed by two urologists and a radiologist to determine if the studies were indicated, appropriately timed, informative, and complete. Our results indicate a high percentage of these examinations are incompletely performed and uninformative and could have been replaced by noninvasive studies. What constitutes a complete retrograde study and when to utilize this examination is discussed.