Study protocol for The GOAL Trial: comprehensive geriatric assessment for frail older people with chronic kidney disease to increase attainment of patient-identified goals-a cluster randomised controlled trial.

BACKGROUND: An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown. METHODS: The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3-5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units. DISCUSSION: This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial's findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.

Effectiveness and patient satisfaction with office hysteroscopic polypectomy in patients with symptomatic endometrial polyps.

Background: Endometrial polyps are a common cause of abnormal uterine bleeding. In-office hysteroscopic management is frequently performed to treat this frequently encountered pathology. Objectives: To evaluate the long-term outcome and patients' satisfaction with office hysteroscopic polypectomy in patients with symptomatic endometrial polyps. Materials and Methods: Retrospective longitudinal observational study of all hysteroscopic polypectomies performed at d'Igualada University Hospital (Barcelona, Spain) between May 2016 and December 2018. The medical records were reviewed, and a telephone interview was conducted with all the patients diagnosed with symptomatic endometrial polyps who underwent outpatient hysteroscopic polypectomy, with the purpose of evaluating the post-procedure symptomatology and satisfaction with the procedure. Main outcomes and results: A total of 848 outpatient hysteroscopies were performed, 379 of which were polypectomies. Of those, 163 procedures were performed in symptomatic patients and were included in the final analysis. The most common symptom among premenopausal patients was abnormal uterine bleeding (84.85%) and in postmenopausal women, postmenopausal bleeding (95.3%). After the procedure, the symptoms resolved or decreased considerably in 66.7% of premenopausal and 93.7% of postmenopausal patients. Additionally, 87.1% of the patients were very satisfied with the procedure. Conclusion: Office hysteroscopic polypectomy is an effective treatment for endometrial polyps with high patient satisfaction reported following the procedure.

Experimental investigation of phase-sensitive amplification of data signals in a four-mode fiber-based PSA.

In this Letter, we investigate the influence of the phase and power of pump and signal waves on the gain of a four-mode phase-sensitive amplifier (PSA) built with a highly nonlinear fiber (HNLF), using a copier + PSA scheme to generate phase- and frequency-correlated idler waves. Using such an amplifier, low-noise amplification of a 10 Gsymbol/s quadrature phase-shift keying (QPSK) signal, with net gain of ∼20 dB and less than 1 dB optical signal-to-noise ratio (OSNR) penalty at a bit error ratio (BER) of 10(-3), was achieved. We also verified an additional net gain of 11.6 dB when switching from phase-insensitive to phase-sensitive operation, which is in good agreement with theoretical predictions of 12 dB.

Renal drug dosing recommendations: evaluation of product information for brands of the same drug.

OBJECTIVES: To review the product information (PI) for various brands of the same generic drugs and investigate the extent to which information is currently available on dosing in renal impairment and the concordance between the dosing recommendations for the same generic drug. METHOD: The Monthly Index of Medical Specialities (MIMS) was examined for 28 generic drugs recommended to be used with caution in renal impairment. For each generic drug all available brands listed as having solid oral dosage form were recorded. For each identified brand, the current PI was consulted and data referring to renal impairment was collated. The dissimilarity between these PI regarding the renal dosage recommendation was determined. RESULTS: There was generally a lack of detailed information in the PI on the use of drugs in patients with renal impairment. The majority of PI documents (88 of 155 PI; 57%) provided quantitative dosage recommendations, but this was often not detailed enough to help users to make an informed decision. For 37 PI documents (24%), an altered dosage regimen was proposed without a quantifiable measure of renal function reported in the dose recommendation. The renal function severity category terms used and the associated quantitative values were also not consistent. It was observed that the recommendations varied among different brands of hydromorphone, morphine, oxycodone, tramadol, metformin and topiramate. CONCLUSION: The reporting of renal function quantification methods, and associated dosage recommendations, in PI requires standardisation to ensure optimal drug dosing. Regularly updating of PI is also necessary.

Dose adjustment guidelines for medications in patients with renal impairment: how consistent are drug information sources?

BACKGROUND: It is known that patients with renal disease are often administered inappropriate dosages of drugs. A lack of quantitative data in the available drug information sources and inconsistency in dosing information may augment the problem of dosing error. AIMS: To determine the concordance among five drug information sources regarding the dosing recommendations provided for drugs considered problematic in patients with renal impairment and to determine the consistency among the sources regarding the definition of renal impairment and categorisation of chronic kidney disease. METHODS: Five standard drug information sources were reviewed for 61 drugs recommended to be used with caution in renal impairment. Information on recommendations for dosage adjustment in renal impairment was extracted and analysed. Further, the definition and classification of renal impairment were recorded. The recommendation for each drug was coded into six different categories and the intersource reliability was calculated. RESULTS: Only slight agreement was observed among the sources (Fleiss Kappa: 0.3). Qualitative data were not well defined, and there was a lack of consistency in quantitative values. Some drugs marked as contraindicated in one source were not mentioned as such in others. Also, drugs considered as not requiring dosage adjustment in one source had explicit recommendations in other sources. The definition and classification of renal impairment differed among the five information sources. CONCLUSIONS: There should be an evidence-based approach to drug dosage adjustment in order to bring uniformity to the recommendations. Regular updating of the content of the drug information sources is also important.

Slope variation and population structure of tree species from different ecological groups in South Brazil

Size structure and spatial arrangement of 13 abundant tree species were determined in a riparian forest fragment inParaná State, South Brazil (23"16'S and 51"01'W). The studied species were Aspidosperma polyneuron Müll. Arg., Astronium graveolens Jacq. and Gallesia integrifolia (Spreng) Harms (emergent species); Alseis floribunda Schott, Ruprechtia laxiflora Meisn. and Bougainvillea spectabilis Willd. (shade-intolerant canopy species); Machaerium paraguariense Hassl, Myroxylum peruiferum L. and Chrysophyllum gonocarpum (Mart. & Eichler ex Miq.) Engl. (shade-tolerant canopy species); Sorocea bonplandii (Baill.) Bürger, Trichilia casaretti C. Dc, Trichilia catigua A. Juss. and Actinostemon concolor (Spreng.) Müll. Arg. (understory small trees species). Height and diameter structures and basal area of species were analyzed. Spatial patterns and slope correlation were analyzed by Moran's / spatial autocorrelation coefficient and partial Mantel test, respectively. The emergent and small understory species showed the highest and the lowest variations in height, diameter and basal area. Size distribution differed among emergent species and also among canopy shade-intolerant species. The spatial pattern ranged among species in all groups, except in understory small tree species. The slope was correlated with spatial pattern for A. polyneuron, A. graveolens, A. floribunda, R. laxiflora, M. peruiferum and T. casaretti. The results indicated that most species occurredin specific places, suggesting that niche differentiation can be an important factor in structuring the tree community.

Visando contribuir para o conhecimento das estratégias devida de espécies em fragmentos florestais, foram determinadas as estruturas de tamanho e espacial de 13 espécies arbóreas do remanescente de floresta ciliar no Estado do Paraná, no Sul do Brasil (23"16'S e 51"01'W). Foram analisadas as espécies: Aspidosperma polyneuron Müll. Arg., Astronium graveolens Jacq. e Gallesia integrifolia (Spreng) Harms, (emergentes); Alseis floribunda Schott, Ruprechtia laxiflora Meisn. e Bougainvillea spectabilis Willd. (dossel, intolerantes à sombra); Machaerium paraguariense Hassl, Myroxylum peruiferum L. e Chrysophyllum gonocarpum (Mart. & Eichler exMiq.) Engl. (dossel, tolerantes à sombra); Sorocea bonplandii (Baill.) Bürger, Trichilia casaretti C. Dc, Trichilia catigua A. Juss. e Actinostemon concolor (Spreng.) Müll. Arg. (subosque). Analisou-se a estrutura de diâmetro de cada espécie. Para a análise do padrão espacial e correlação com adeclividade foram utilizados o Índice de Autocorrelação espacial de Moran e o Teste Parcial de Mantel, respectivamente. Os grupos das árvores emergentes e das espécies de subosque apresentaram as maiores e as menores variações na altura e no diâmetro e maior e menor área basal, respectivamente. Diferenças nas estruturas de diâmetro foram observadas entre as espécies emergentes e entre as espécies de dossel intolerantes à sombra. O padrão espacial variou entre as espécies de todos os grupos, exceto as espécies de subosque tolerantes à sombra. A topografia estava relacionada com a distribuição espacial de A. polyneuron, A. graveolens, A. floribunda, R. laxiflora, M. peruiferum e T. casaretti. A análise dos resultados indicou que para cada espécie a maioria dos indivíduos ocorriam em locais específicos, sugerindo que a diferenciação de nicho pode estar relacionada à estruturação desta comunidade arbórea.

Slope variation and population structure of tree species from different ecological groups in South Brazil.

Size structure and spatial arrangement of 13 abundant tree species were determined in a riparian forest fragment in Paraná State, South Brazil (23°16'S and 51°01'W). The studied species were Aspidosperma polyneuron Müll. Arg., Astronium graveolens Jacq. and Gallesia integrifolia (Spreng) Harms (emergent species); Alseis floribunda Schott, Ruprechtia laxiflora Meisn. and Bougainvillea spectabilis Willd. (shade-intolerant canopy species); Machaerium paraguariense Hassl, Myroxylum peruiferum L. and Chrysophyllum gonocarpum (Mart. & Eichler ex Miq.) Engl. (shade-tolerant canopy species); Sorocea bonplandii (Baill.) Bürger, Trichilia casaretti C. Dc, Trichilia catigua A. Juss. and Actinostemon concolor (Spreng.) Müll. Arg. (understory small trees species). Height and diameter structures and basal area of species were analyzed. Spatial patterns and slope correlation were analyzed by Moran's / spatial autocorrelation coefficient and partial Mantel test, respectively. The emergent and small understory species showed the highest and the lowest variations in height, diameter and basal area. Size distribution differed among emergent species and also among canopy shade-intolerant species. The spatial pattern ranged among species in all groups, except in understory small tree species. The slope was correlated with spatial pattern for A. polyneuron, A. graveolens, A. floribunda, R. laxiflora, M. peruiferum and T. casaretti. The results indicated that most species occurred in specific places, suggesting that niche differentiation can be an important factor in structuring the tree community.

Protein kinase C-zeta activation markedly enhances beta-cell proliferation: an essential role in growth factor mediated beta-cell mitogenesis.

OBJECTIVE: Diabetes results from a deficiency of functional beta-cells. Previous studies have identified hepatocyte growth factor (HGF) and parathyroid hormone-related protein (PTHrP) as two potent beta-cell mitogens. The objective of this study is to determine 1) whether HGF and PTHrP have additive/synergistic effects on beta-cell growth and proliferation; 2) the signaling pathways through which these growth factors mediate beta-cell mitogenesis; and 3) whether activation of this/these signaling pathway(s) enhances human beta-cell replication. RESEARCH DESIGN AND METHODS: We generated and phenotypically analyzed doubly transgenic mice overexpressing PTHrP and HGF in the beta-cell. INS-1 and primary mouse and human islet cells were used to identify mitogenic signaling pathways activated by HGF and/or PTHrP. RESULTS: Combined overexpression of HGF and PTHrP in the beta-cell of doubly transgenic mice did not result in additive/synergistic effects on beta-cell growth and proliferation, suggesting potential cross-talk between signaling pathways activated by both growth factors. Examination of these signaling pathways in INS-1 cells revealed atypical protein kinase C (PKC) as a novel intracellular target activated by both HGF and PTHrP in beta-cells. Knockdown of PKC zeta, but not PKC iota/lambda, expression using specific small-interfering RNAs blocked growth factor-induced INS-1 cell proliferation. Furthermore, adenovirus-mediated delivery of kinase-dead PKC zeta completely inhibited beta-cell proliferation in primary islet cells overexpressing PTHrP and/or HGF. Finally, adenovirus-mediated delivery of constitutively active PKC zeta in mouse and human primary islet cells significantly enhanced beta-cell proliferation. CONCLUSIONS: PKC zeta is essential for PTHrP- and HGF-induced beta-cell proliferation. PKC zeta activation could be useful in therapeutic strategies for expanding beta-cell mass in vitro and in vivo.

Acute renal failure in a patient with paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder characterized by low-grade, chronic hemolytic anemia accompanied by either thrombocytopenia or leucopenia. Kidney involvement is usually benign and secondary to chronic tubular deposition of hemosiderin. Acute renal failure may occur in association with a hemolytic crisis. We report the case of a 70-year-old Caucasian woman with PNH who developed reversible acute renal failure requiring hemodialysis following a gastointestinal illness. Renal biopsy demonstrated acute tubular necrosis with considerable hemosiderin deposition, but no evidence of vascular thrombosis.

Renal sarcoidosis in Christchurch, New Zealand 1970-1998.

AIM: To identify patients presenting to a nephrologist in whom a diagnosis of sarcoidosis could be made, to assess the relevant causes of renal involvement and to review treatment and long-term follow-up of this group. METHOD: A retrospective review of the computer database PROTON for patients given the diagnosis of sarcoidosis, followed by a case note review of identified patients with respect to the mode of presentation, clinical and laboratory features, treatment and subsequent follow-up. RESULTS: Nineteen patients (15 males) were identified, mean age 45 years, all were Caucasian, and follow-up was four months to 26 years (mean 9.3 years). Most common mode of presentation was acute renal failure (11) during spring/summer (14). Evidence for systemic disease was present in all patients. Mean plasma creatinine on presentation was 0.52 mmol/L and calcium 3.01 mmol/L. Hypercalcaemia was present in 60%. Kidney biopsy was performed in seven patients with the predominant findings of tubular atrophy and interstitial fibrosis; significant granulomata were present in only two. Treatment in all patients was with corticosteroids with good result. Mean long term plasma creatinine was 0.17 mmol/L at 9.3 years. Steroid withdrawal was attempted in all patients, successful in five, with the mean time to relapse of five months in the remaining 14. Mean steroid dose in this group was 7.6 mg on long term follow-up. CONCLUSIONS: Sarcoidosis causes renal dysfunction mainly through altered calcium metabolism. Treatment with corticosteroids is successful in improving renal function, but relapse is common on steroid withdrawal and prolonged treatment is necessary for disease control.

[Endocarditis caused by Brucella melitensis on a mitral valve prosthesis presenting as an ischemic cerebrovascular accident]. / Endocarditis por Brucella melitensis sobre válvula mitral protésica que comienza como accidente cerebrovascular isquémico.

A new case of endocarditis by Brucella melitensis on a mitral valve prosthesis in a 15 year old patient, whose first manifestation was an ischemic cerebrovascular accident is reported. The patient presented with daily fever only two months later. Medical treatment alone was not sufficient to avoid valvular failure and substitution of the prosthesis was required. The clinical manifestations and complications of this infrequent condition is discussed. Treatment, which often requires the combination of surgery and antibiotics administered over a prolonged period, is highly recommended.