Long-term use of 5-alpha-reductase inhibitors is safe and effective in men on active surveillance for prostate cancer.

BACKGROUND: Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS. MATERIALS/SUBJECTS AND METHODS: The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995-2016). Pathologic, grade, and volume progression were the primary end points. Kaplan-Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time. RESULTS: The cohort included 288 men with median follow-up of 82 months (interquartile range: 37-120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p < 0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p < 0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR: 2.65; CI: 1.65-4.24), grade progression (HR: 2.75; CI: 1.49-5.06), and volume progression (HR: 3.15; CI: 1.78-5.56). The frequency of progression to high-grade (Grade Group 4-5) tumors was not significantly different between the groups. CONCLUSIONS: Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4-5 disease.

A multi-institutional randomized controlled trial comparing first-generation transrectal high-resolution micro-ultrasound with conventional frequency transrectal ultrasound for prostate biopsy.

Objectives: To study high-frequency 29 MHz transrectal side-fire micro-ultrasound (micro-US) for the detection of clinically significant prostate cancer (csPCa) on prostate biopsy, and validate an image interpretation protocol for micro-US imaging of the prostate. Materials and methods: A prospective randomized clinical trial was performed where 1676 men with indications for prostate biopsy and without known prostate cancer were randomized 1:1 to micro-US vs conventional end-fire ultrasound (conv-US) transrectal-guided prostate biopsy across five sites in North America. The trial was split into two phases, before and after training on a micro-US image interpretation protocol that was developed during the trial using data from the pre-training micro-US arm. Investigators received a standardized training program mid-trial, and the post-training micro-US data were used to examine the training effect. Results: Detection of csPCa (the primary outcome) was no better with the first-generation micro-US system than with conv-US in the overall population (34.6% vs 36.6%, respectively, P = .21). Data from the first portion of the trial were, however, used to develop an image interpretation protocol termed PRI-MUS in order to address the lack of understanding of the appearance of cancer under micro-US. Micro-US sensitivity in the post-training group improved to 60.8% from 24.6% (P < .01), while specificity decreased (from 84.2% to 63.2%). Detection of csPCa in the micro-US arm increased by 7% after training (32% to 39%, P < .03), but training instituted mid-trial did not affect the overall results of the comparison between arms. Conclusion: Micro-US provided no clear benefit over conv-US for the detection of csPCa at biopsy. However, it became evident during the trial that training and increasing experience with this novel technology improved the performance of this first-generation system.

Task shifting of cardiovascular risk assessment and communication by nurses for primary and secondary prevention of cardiovascular diseases in a tertiary health care setting of Northern India.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality in India. CVDs are to a large extent preventable with the availability of wide range of interventions focusing on primary and secondary prevention. However human resource deficit is the biggest challenge for implementing these prevention programs. Task shifting of the cardiovascular risk assessment and communication to nurses can be one of the most viable and sustainable option to run prevention programs. METHODS: The study was quasi experimental in nature with 1 year follow up to determine the effect of CVD risk assessment and communication by nurses with the help of risk communication package on primary and secondary prevention of CVDs. The study was done in the outpatient departments of a tertiary health care center of Northern India. All the nurses (n = 16) working in selected OPDs were trained in CVD risk assessment and communication of risk to the patients. A total of 402 patients aged 40 years and above with hypertension (HTN) were recruited for primary prevention of CVDs from medicine and allied OPDs, whereas 500 patients who had undergone CABG/PTCA were recruited from cardiology OPDs for secondary prevention of CVDs and were randomized to intervention (n = 250) and comparison group (n = 250) by using block randomization. CVD risk modification and medication adherence were the outcomes of interest for primary and secondary prevention of CVDs respectively. RESULTS: The results revealed high level of agreement (k = 0.84) between the risk scores generated by nurses with that of investigator. In the primary prevention group, there were significantly higher proportion of participants in the low risk category (70%) as compared to baseline assessment (60.6%) at 1 year follow up. Whereas in secondary prevention group the mean medication adherence score among intervention group participants (7.60) was significantly higher than that of the comparison group (5.96) with a large effect size of 1.1.(p < 0.01). CONCLUSION: Nurse led intervention was effective in risk modification and improving medication adherence among subjects for primary and secondary prevention of CVDs respectively. TRIAL REGISTRATION: Trial registration no CTRI/2018/01/011372 [Registered on: 16/01/2018] Trial Registered Retrospectively.

Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

MR imaging-guided prostate interventional imaging: Ready for a clinical use?

Prostate interventional magnetic resonance imaging (MRI) is now routinely performed in many centers. Its more widespread acceptance is limited by the cost of the use of MRI largely related to the long duration time of the procedures. However, the benefit of a robotic assistance has generated a new interest, because it substantially shortens the procedure time, while improving the accuracy. MRI-guided biopsy is considered as an appealing alternative to transrectal ultrasound (TRUS)-guided fusion biopsy, given the limitations of TRUS-MRI image registration systems. MRI-guided focal treatment also benefits from robotic assistance and from the unique property of MRI, which allows the measurement of the temperature in real-time during tumor ablation. The transrectal and transperineal approaches can be used and the respective indications of each pathway will depend on several factors, including the location of the tumor and the examination time, which will condition the occupation time of the MR room, a major factor influencing the overall cost of MRI-guided procedures. This review addresses the current practice of prostate MRI-guided interventional procedures and potential future applications.

Evaluating human rabies control in Asia: using 'One Health' principles to assess control programmes for rabies.

Rabies is a global issue, and kills tens of thousands of people every year, despite being a preventable disease. The goal of the World Health Organization (WHO) and the World Organisation for Animal Health (OIE) to eliminate dog-mediated rabies by 2030 requires serious collaborative efforts across Ministries and countries. This cross-sector cooperation includes, but is not limited to, physicians, veterinarians, local authorities, local communities and the media; in other words, a 'One Health' approach. Countries where human rabies has been successfully eliminated still require constant vigilance, in terms of regulations on companion animal ownership and vaccination, the movement of animals from countries where the disease still exists, and the continued raising of public awareness. Rabies-endemic countries need to refocus their efforts towards eliminating the disease once and for all, by working together and sharing their knowledge, experiences and efforts. Rabies control programmes require the efficient management of resources, and surveillance programmes do not need to be specific to one disease. Governments must play a more proactive role by enforcing legislation and allocating funds and resources to help to eliminate human rabies by 2030 throughout the world.

La rage est un problème mondial qui fait des dizaines de milliers de victimes humaines chaque année alors même qu'elle est une maladie évitable. L'objectif que se sont fixé l'Organisation mondiale de la santé (OMS) et l'Organisation mondiale de la santé animale (OIE) d'éliminer la rage transmise par les chiens d'ici 2030 nécessite qu'une véritable collaboration soit en place entre ministères et entre pays différents. Cette coopération intersectorielle comprend la participation de médecins et de vétérinaires ainsi que des administrations et communautés locales et des médias, entre autres intervenants ; autrement dit, il s'agit d'une approche « Une seule santé ¼. Les pays ayant réussi à éliminer la rage humaine doivent continuer à exercer une vigilance permanente, en réglementant la possession et la vaccination d'animaux de compagnie, en surveillant les mouvements d'animaux provenant de pays où la maladie est toujours présente et en sensibilisant sans relâche les populations. Les pays où la rage est endémique doivent recentrer leurs efforts sur l'élimination totale et définitive de la maladie en collaborant entre eux et en partageant leurs connaissances, leurs expériences et leurs efforts. Les programmes de lutte contre la rage nécessitent une gestion efficiente des ressources tandis que les programmes de surveillance ne sont pas nécessairement spécifiques à une seule maladie. Les gouvernements doivent jouer un rôle plus proactif aussi bien en matière de législation que d'allocation des fonds et des ressources afin de contribuer à l'élimination de la rage humaine dans le monde d'ici 2030.

La rabia es un problema planetario, una enfermedad que, pese a ser prevenible, mata a decenas de miles de personas al año. El objetivo que persiguen la Organización Mundial de la Salud (OMS) y la Organización Mundial de Sanidad Animal (OIE), esto es, haber eliminado la rabia transmitida por perros para 2030, exige una seria labor de colaboración entre ministerios y países. En esta cooperación intersectorial deben participar, entre otras instancias, médicos, veterinarios, autoridades locales, comunidades locales y medios de comunicación, lo que supone, dicho de otro modo, aplicar los planteamientos de «Una sola salud¼. Los países donde ya se ha logrado eliminar la rabia humana siguen requiriendo una vigilancia constante, que se plasma en la aplicación de reglamentos sobre la tenencia y vacunación de animales de compañía y el movimiento de animales desde países donde aún existe la enfermedad, junto con una continua labor de sensibilización pública. Los países con rabia endémica deben reorientar sus esfuerzos para eliminar la enfermedad de una vez por todas, trabajando conjuntamente y compartiendo conocimientos, experiencias y actividades. Los programas de lucha antirrábica requieren una gestión eficiente de los recursos, y en este sentido no es preciso que los programas de vigilancia estén centrados específicamente en una sola enfermedad. Los gobiernos deben cumplir una función más activa y resolutiva, haciendo cumplir las leyes y destinando fondos y recursos al objetivo de haber eliminado la rabia humana en todo el mundo para 2030.

Patient selection for prostate focal therapy in the era of active surveillance: an International Delphi Consensus Project.

BACKGROUND: Whole-gland extirpation or irradiation is considered the gold standard for curative oncological treatment for localized prostate cancer, but is often associated with sexual and urinary impairment that adversely affects quality of life. This has led to increased interest in developing therapies with effective cancer control but less morbidity. We aimed to provide details of physician consensus on patient selection for prostate focal therapy (FT) in the era of contemporary prostate cancer management. METHODS: We undertook a four-stage Delphi consensus project among a panel of 47 international experts in prostate FT. Data on three main domains (role of biopsy/imaging, disease and patient factors) were collected in three iterative rounds of online questionnaires and feedback. Consensus was defined as agreement in ⩾80% of physicians. Finally, an in-person meeting was attended by a core group of 16 experts to review the data and formulate the consensus statement. RESULTS: Consensus was obtained in 16 of 18 subdomains. Multiparametric magnetic resonance imaging (mpMRI) is a standard imaging tool for patient selection for FT. In the presence of an mpMRI-suspicious lesion, histological confirmation is necessary prior to FT. In addition, systematic biopsy remains necessary to assess mpMRI-negative areas. However, adequate criteria for systematic biopsy remains indeterminate. FT can be recommended in D'Amico low-/intermediate-risk cancer including Gleason 4+3. Gleason 3+4 cancer, where localized, discrete and of favorable size represents the ideal case for FT. Tumor foci <1.5 ml on mpMRI or <20% of the prostate are suitable for FT, or up to 3 ml or 25% if localized to one hemi-gland. Gleason 3+3 at one core 1mm is acceptable in the untreated area. Preservation of sexual function is an important goal, but lack of erectile function should not exclude a patient from FT. CONCLUSIONS: This consensus provides a contemporary insight into expert opinion of patient selection for FT of clinically localized prostate cancer.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Follow-up modalities in focal therapy for prostate cancer: results from a Delphi consensus project.

INTRODUCTION: Focal therapy can offer the middle ground for treatment between active surveillance and radical therapy in patients with low- and intermediate-risk prostate cancer. Factors that prohibit focal therapy from being standard of care are numerous. Several consensus projects have been conducted to position the utilization of imaging and trial design in focal therapy. However, the literature is still scarce on patient follow-up after focal therapy. For these reasons, an international multidisciplinary consensus project was established in order to reach consensus about a uniform follow-up protocol after focal therapy. OBJECTIVE: To standardize patient follow-up after focal therapy. MATERIALS AND METHODS: A literature study was performed, and a questionnaire was constructed. The questionnaire was sent out to 76 participants (70 % urologists, 28 % radiologists and 2 % biomedical engineers) in three consecutive rounds according to the Delphi method. In each round, the panelists were presented with the results of the previous round. Participants each had the opportunity to adapt, delete or add questions. The topics discussed pertaining to follow-up after focal therapy were as follows: (1) general,(2) biopsies, (3) PSA, (4) digital rectal examination (DRE), (5) imaging, (6) quality of life (QoL) and (7) registration and pooling of data. The project was concluded with a face-to-face meeting in which final conclusions were formulated. RESULTS: The follow-up after focal therapy should be a minimum of 5 years. The following modalities should be included in assessing post-treatment outcomes: multiparametric MRI (mpMRI), biopsies, assessment of erectile function, QoL, urinary symptoms and incontinence. A systematic 12-core TRUS biopsy combined with 4-6 targeted biopsy cores of the treated area and any suspicious lesion(s) should be performed after 1 year, and thereafter only when there is suspicion on imaging. The ideal way to perform targeted biopsies is to use TRUS-MRI fusion technology. PSA should be performed for research purposes, in the first year, every 3 months, and after the first year, every 6 months. mpMRI is the optimal imaging modality for follow-up after focal therapy. On a 1.5T scanner, an endorectal coil is strongly advised by the panel, whereas on a 3T machine, it is optional, however, it will improve image quality. The following sequences should be included: T2WI, DWI including high b values of >1,000 and ADC maps of DWI, DCE and T1WI. Imaging should be performed at 6 months and at 1 year following treatment; after the first year post-treatment, it should be performed every year until 5 years following treatment. All data should ideally be pooled in a common global database. CONCLUSION: Focal therapy is a relatively new form of treatment for prostate cancer. In order to include focal therapy as a standard of care treatment, consistent follow-up is necessary. By implementing the results of this consensus study, focal therapy users will be able to provide important and standardized outcome data.

Antagonistic and antimicrobial activities of some bacterial isolates collected from soil samples.

Thirty seven bacterial cultures isolated from soil samples obtained from different locations were tested for their antagonistic activity against some fungal pathogens, viz., Sclerotium rolfsii, Fusarium oxysporum and Rhizoctonia solani, causal agents of collar rot of sunflower, wilts and root rots, respectively. Among them, 5 bacterial strains, viz., A1 6 (Bacillus sphaericus), K1 24 (Pseudomonas fluorescens), M1 42 (Bacillus circulans), M1 66 (Bacillus brevis) and T1 22 (Bacillus brevis) showed positive antagonistic activity. M1 66 was the most effective in inhibiting mycelial growth of S. rolfsii in vitro followed by M1 42, T1 22, K1 24 and A1 6. Only one bacterial strain i.e. M1 42 exhibited antagonistic activity against F. oxysporum, and none of the bacterial strains gave positive activity against R. solani. Furthermore, antimicrobial activities of all the 5 strains were checked against different test organisms. These strains showed their extensive inhibition effect particularly against gram-positive test bacteria (Staphylococcus aureus and Bacillus subtilis) and the test fungal strain (Candida albicans). On the other hand, B. brevis M1 66 and B. brevis T1 22 strains had an inhibitory effect against gram positive and gram-negative test bacteria (Escherichia coli and Proteus vulgaris) as well as the test fungal strain.

Prenatal ultrasound findings of lissencephaly associated with Miller-Dieker syndrome and comparison with pre- and postnatal magnetic resonance imaging.

OBJECTIVE: To report on the prenatal ultrasound findings in fetuses with lissencephaly associated with Miller-Dieker syndrome (MDS) and to compare these findings with those of magnetic resonance imaging (MRI). METHODS: Cases of MDS confirmed by postnatal chromosome microdeletion analysis were identified through review of patient records. Prenatal ultrasound scans were reviewed retrospectively by two radiologists. For cerebral cortical development, the Sylvian, parieto-occipital and calcarine fissures, and the cingulate sulcus and sulci over the cerebral convexity were evaluated. If one or more of these fissures or sulci were not visualized at the expected gestational age or their appearance was abnormal for gestational age, cortical development was considered delayed. Prenatal and postnatal MRI examinations were reviewed by a pediatric neuroradiologist. RESULTS: There were seven cases of MDS. In three cases, the prenatal diagnosis of agyria/lissencephaly was prospectively suspected by ultrasound at 23, 26 and 30 weeks, and subsequently confirmed by prenatal MRI. When we retrospectively reviewed the prenatal ultrasound scans of all fetuses, all had delayed cortical development identified on ultrasound performed after 23 weeks' gestation. In all cases the Sylvian fissure was abnormal on both ultrasound and MRI. In one fetus, a normal cortical appearance for gestational age was seen at the initial 20-week ultrasound examination, but delayed cortical development was identified at a 24-week scan. Mild ventriculomegaly was seen in six fetuses and dysgenesis of the corpus callosum in one. Extracranial abnormalities were detected in five fetuses. Delayed cortical development was seen in two fetuses with mild ventriculomegaly, but no other fetal anomalies. CONCLUSIONS: In fetuses with MDS, delayed cortical development can be suspected on ultrasound as early as 23 weeks' gestation. This finding warrants further investigations including MRI and FISH analysis for chromosome 17p13.3 deletion.

Pelvic lipomatosis presenting as uraemic encephalopathy.

Pelvic lipomatosis is a benign disorder of unknown aetiology, characterised by deposition of mature fat in the pelvis. It has a variable natural history, manifesting either with symptoms attributable to the lower urinary tract or varying degrees of renal failure. Owing to the mild, non-specific initial symptoms and slow progression, presentation is delayed and patients are often lost to follow-up, only to present with advanced renal failure later on. We report a case of a young patient with pelvic lipomatosis who, after an initial diagnosis, was lost to follow-up for several years and then presented with uraemic encephalopathy. The case highlights the importance of regular follow-up and an early intervention before irreversible changes occur.