Deficiencies in health-related quality-of-life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016.

Quality of life (QoL) is a relevant end point and a topic of growing interest by both scientific community and regulatory authorities. Our aim was to review QoL prevalence as an end point in cancer phase III trials published in major journals and to evaluate QoL reporting deficiencies in terms of under-reporting and delay of publication. All issues published between 2012 and 2016 by 11 major journals were hand-searched for primary publications of phase III trials in adult patients with solid tumors. Information about end points was derived from paper and study protocol, when available. Secondary QoL publications were searched in PubMed. In total, 446 publications were eligible. In 210 (47.1%), QoL was not included among end points. QoL was not an end point in 40.1% of trials in the advanced/metastatic setting, 39.7% of profit trials and 53.6% of non-profit trials. Out of 231 primary publications of trials with QoL as secondary or exploratory end point, QoL results were available in 143 (61.9%). QoL results were absent in 37.6% of publications in the advanced/metastatic setting, in 37.1% of profit trials and 39.3% of non-profit trials. Proportion of trials not including QoL as end point or with missing QoL results was relevant in all tumor types and for all treatment types. Overall, 70 secondary QoL publications were found: for trials without QoL results in the primary publication, probability of secondary publication was 12.5%, 30.9% and 40.3% at 1, 2 and 3 years, respectively. Proportion of trials not reporting QoL results was similar in trials with positive results (36.5%) and with negative results (39.4%), but the probability of secondary publication was higher in positive trials. QoL is not included among end points in a relevant proportion of recently published phase III trials in solid tumors. In addition, QoL results are subject to significant under-reporting and delay in publication.

Performance of the Multidimensional Geriatric Assessment and Multidimensional Prognostic Index in predicting negative outcomes in older adults with cancer.

The Multidimensional Geriatric Assessment (MGA) is currently used for assessing geriatric oncological patients, but a new prognostic index - the Multidimensional Prognostic Index (MPI) - has a demonstrated prognostic value in cancer patients too. The present work was designed to compare the MPI and MGA as predictors of 12-month mortality. 160 patients ≥70 years old with locally-advanced or metastatic solid cancers consecutively joining our Geriatric Oncology Program were administered a Comprehensive Geriatric Assessment to calculate their MGA and MPI scores. SETTINGS: Geriatric Clinic, Geriatric Surgery Clinic, Medical Oncology Unit, Padova Hospital, Italy. Using Cohen's Kappa coefficient, there was a poor concordance between the MPI and MGA. Severe MPI being associated with a higher mortality risk than Frail in the MGA. The ROC curves indicated that the MPI had a greater discriminatory power for 12-month mortality than the MGA. In our population of elderly cancer patients, the MPI performed better than the MGA in predicting mortality. Further evidence from larger prospective trials is needed to establish whether other geriatric scales, such as the GDS and CIRS-SI, could enhance the value of prognostic indexes applied to elderly cancer patients.

Monocytes of patients with amyotrophic lateral sclerosis linked to gene mutations display altered TDP-43 subcellular distribution.

AIMS: Cytoplasmic accumulation of the nuclear protein transactive response DNA-binding protein 43 (TDP-43) is an early determinant of motor neuron degeneration in most amyotrophic lateral sclerosis (ALS) cases. We previously disclosed this accumulation in circulating lymphomonocytes (CLM) of ALS patients with mutant TARDBP, the TDP-43-coding gene, as well as of a healthy individual carrying the parental TARDBP mutation. Here, we investigate TDP-43 subcellular localization in CLM and in the constituent cells, lymphocytes and monocytes, of patients with various ALS-linked mutant genes. METHODS: TDP-43 subcellular localization was analysed with western immunoblotting and immunocytofluorescence in CLM of healthy controls (n = 10), patients with mutant TARDBP (n = 4, 1 homozygous), valosin-containing protein (VCP; n = 2), fused in sarcoma/translocated in liposarcoma (FUS; n = 2), Cu/Zn superoxide dismutase 1 (SOD1; n = 6), chromosome 9 open reading frame 72 (C9ORF72; n = 4), without mutations (n = 5) and neurologically unaffected subjects with mutant TARDBP (n = 2). RESULTS: TDP-43 cytoplasmic accumulation was found (P < 0.05 vs. controls) in CLM of patients with mutant TARDBP or VCP, but not FUS, in line with TDP-43 subcellular localization described for motor neurons of corresponding groups. Accumulation also characterized CLM of the healthy individuals with mutant TARDBP and of some patients with mutant SOD1 or C9ORF72. In 5 patients, belonging to categories described to carry TDP-43 mislocalization in motor neurons (3 C9ORF72, 1 TARDBP and 1 without mutations), TDP-43 cytoplasmic accumulation was not detected in CLM or in lymphocytes but was in monocytes. CONCLUSIONS: In ALS forms characterized by TDP-43 mislocalization in motor neurons, monocytes display this alteration, even when not manifest in CLM. Monocytes may be used to support diagnosis, as well as to identify subjects at risk, of ALS and to develop/monitor targeted treatments.

Efficacy of biofeedback plus transanal stimulation in the management of pelvic floor dyssynergia: a randomized trial.

BACKGROUND: The therapy of pelvic floor dyssynergia is mostly conservative and is based on a high-fiber diet, physical activity and biofeedback training. Our aim was to compare the outcome of biofeedback (manometric-assisted pelvic relaxation and simulated defecation training) plus transanal electrostimulation with standard therapy (diet, exercise, laxatives). METHODS: Clinical, physiologic and quality of life [patient assessment of constipation quality of life (PAC-QOL)] measures, anorectal manometry and balloon expulsion test results were collected prospectively at baseline, at the end of the treatment and 6 months after treatment. Primary outcome was the modification of the Wexner score for defecation (WS) and the obstructed defecation score (ODS). Secondary outcomes were the modifications of anorectal manometry pattern and quality of life after treatment. RESULTS: The mean WS and ODS decreased significantly in the EMG biofeedback group: The WS decreased from 16.7 ± 4 to 10 ± 3.5 p < 0.0102, and the ODS decreased from 18.3 ± 5.5 to 5.7 ± 1.8, p < 0.0001. Besides, WS and ODS did not change significantly in the control group. The PAC-QOL score improved significantly from 61 ± 8.6 to 23 ± 4.8 (p < 0.0001) in the EMG biofeedback group; otherwise, the PAC-QOL score did not change significantly in the control group. CONCLUSIONS: Biofeedback therapy plus transanal electrostimulation provided sustained improvement in bowel symptoms and anorectal function in constipated subjects with dyssynergic defecation, whereas standard therapy was largely ineffective.

Focus on abdominal rectopexy for full-thickness rectal prolapse: meta-analysis of literature.

BACKGROUND: Laparoscopic rectopexy to treat full-thickness rectal prolapse has proven short-term benefits, but there are few long-term follow-up and functional outcome data available. Using meta-analysis techniques, this study was designed to evaluate long-term results of open and laparoscopic abdominal procedures to treat full-thickness rectal prolapse in adults. METHODS: A literature review was performed using the National Library of Medicine's PubMed database. All articles on abdominal rectopexy patients with a follow-up longer than 16 months were considered. The primary end point was recurrence of rectal prolapse, and the secondary end points were improvement in incontinence and constipation. A random effect model was used to aggregate the studies reporting these outcomes, and heterogeneity was assessed. RESULTS: Eight comparative studies, consisting of a total of 467 patients (275 open and 192 laparoscopic), were included. Analysis of the data suggested that there is no significant difference in recurrence, incontinence and constipation improvement between laparoscopic abdominal rectopexy and open abdominal rectopexy. Considering non-comparative trials, the event rate for recurrence was similar in open and laparoscopic suture rectopexy studies and in open and laparoscopic mesh rectopexy trials. Improvement in constipation after the intervention was not statistically significant except for open mesh repair; postoperative improvement in incontinence was statistically significant after laparoscopic procedures and open mesh rectopexy. CONCLUSIONS: Laparoscopic abdominal rectopexy is a safe and feasible procedure, which may compare equally with the open technique with regard to recurrence, incontinence and constipation. However, large-scale randomized trials, with comparative, strong methodology, are still needed to identify outcome measures accurately.

The obligation to say 'Thank you': heart transplant recipients' experience of writing to the donor family.

Transplant recipients are encouraged to write anonymous thank-you letters to the donor family. We prospectively explored heart transplant recipients' embodied responses to the 'obligation' to write a thank-you letter using audio/video-taped open-ended interviews (N = 27). Fifteen of the 19 participants, who wrote letters to the donor family, expressed or visually revealed significant distress about issues such as the obligation to write anonymously and the inadequacy of the 'thank-you'. Writing the thank-you letter is not a neutral experience for heart transplant recipients. Rethinking the obligatory practice regarding the thank-you letter and developing the necessary support for the recipient through this process is necessary.

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital.

BACKGROUND: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. OBJECTIVE: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. METHODS: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. RESULTS: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). CONCLUSIONS: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

Sympathectomy alters bone architecture in adult growing rats.

Sympathetic nervous system (SNS) fibres and alpha- and beta-receptors are present in bone, indicating that the SNS may participate in bone metabolism. The importance of these observations is controversial because stimulation or inhibition of the SNS has had various effects upon both anabolic and catabolic activity in this tissue. In this study we evaluated the effects of pharmacological sympathectomy, using chronic treatment of maturing male rats with 40 mg of guanethidine/kg i.p., upon various parameters in bone. Double labelling with tetracycline injection was also performed 20 and 2 days before sacrifice. Bone mass, mineral content, density and histomorphometric characteristics in different skeletal regions were determined. Bone metabolic markers included urinary deoxypyridinoline and serum osteocalcin measurements. Guanethidine significantly reduced the accretion of lumbar vertebral bone and of mineral content and density, compared to controls. Femoral bone mineral content and density were also significantly reduced, compared to controls. Histomorphometric analyses indicated these effects were related to a reduction of cortical bone and mineral apposition rate at femoral diaphysials level. Both markers of bone metabolism were reduced in controls as they approached maturity. Guanethidine significantly decreased serum osteocalcin compared to controls, while urinary deoxypyridinoline was unchanged. These data indicate that guanethidine-induced sympathectomy caused a negative balance of bone metabolism, leading to decreased mass by regulating deposition rather than resorption during modeling and remodeling of bone.

Canadian Society of Transplantation Members' Views on Anonymity in Organ Donation and Transplantation.

BACKGROUND: Anonymity has been central to medical, psychosocial, and societal practices in organ donation and transplantation. The purpose of this investigation was to explore transplant professionals' views on anonymity in the context of organ transplantation. METHODS: The study consisted of an electronic 18-item survey distributed to the Canadian Society of Transplantation membership, asking about anonymity vs open communication/contact between organ recipients and donor families. RESULTS: Of the 541 members surveyed, 106 replied. Among respondents, 71% felt that organ recipients and donor families should only communicate anonymously, yet 47% felt that identifying information could be included in correspondence between consenting recipients and donor families. When asked whether organ recipients and donor families should be allowed to meet, 53% of respondents agreed, 27% disagreed, and 20% neither agreed nor disagreed. With social media facilitating communication and eliminating the ability to maintain donor/recipient anonymity, 38% of respondents felt that a reexamination of current policies and practices pertaining to anonymity was necessary. CONCLUSION: In conclusion, there was no dominant position on the issue of anonymity/communication between donor families and transplant recipients. Further research and discussion concerning the views of healthcare professionals, organ recipients, and donor families on the mandate of anonymity is needed and may influence future policy.

Neurological consultations and diagnoses in a large, dedicated COVID-19 university hospital / Consultas neurológicas e diagnósticos em um grande hospital universitário dedicado a COVID-19

ABSTRACT Background: More than one-third of COVID-19 patients present neurological symptoms ranging from anosmia to stroke and encephalopathy. Furthermore, pre-existing neurological conditions may require special treatment and may be associated with worse outcomes. Notwithstanding, the role of neurologists in COVID-19 is probably underrecognized. Objective: The aim of this study was to report the reasons for requesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bed COVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosis was confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurology consultations between March 23rd and May 23rd, 2020 were analyzed. Neurologists performed the neurological exam, assessed all available data to diagnose the neurological condition, and requested additional tests deemed necessary. Difficult diagnoses were established in consensus meetings. After diagnosis, neurologists were involved in the treatment. Results: Neurological consultations were requested for 89 out of 1,208 (7.4%) inpatient COVID admissions during that period. Main neurological diagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurological diseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brain lesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Most neurological consultations in a COVID-19-dedicated hospital were requested for severe conditions that could have an impact on the outcome. First-line doctors should be able to recognize neurological symptoms; neurologists are important members of the medical team in COVID-19 hospital care.

RESUMO Introdução: Mais de um terço dos pacientes com COVID-19 apresentam sintomas neurológicos que variam de anosmia a AVC e encefalopatia. Além disso, doenças neurológicas prévias podem exigir tratamento especial e estar associadas a piores desfechos. Não obstante, o papel dos neurologistas na COVID-19 é provavelmente pouco reconhecido. Objetivo: O objetivo deste estudo foi relatar os motivos para solicitar consultas neurológicas por clínicos e intensivistas em um hospital dedicado à COVID-19. Métodos: Estudo retrospectivo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brasil, um centro dedicado à COVID-19 com 900 leitos (incluindo 300 leitos para unidades de terapia intensiva). O diagnóstico de COVID-19 foi confirmado por SARS-CoV-2-RT-PCR em swabs nasais. Todas as interconsultas de neurologia hospitalar entre 23 de março e 23 de maio de 2020 foram analisadas. Os neurologistas realizaram o exame neurológico, avaliaram todos os dados disponíveis para diagnosticar a patologia neurológica e solicitaram exames adicionais conforme necessidade. Diagnósticos difíceis foram estabelecidos em reuniões de consenso. Após o diagnóstico, os neurologistas participaram da condução dos casos. Resultados: Foram solicitadas consultas neurológicas para 89 de 1.208 (7,4%) em pacientes internados por COVID-19 durante o período. Os principais diagnósticos neurológicos incluíram: encefalopatia (44,4%), acidente vascular cerebral (16,7%), doenças neurológicas prévias (9,0%), crises epilépticas (9,0%), transtornos neuromusculares (5,6%), outras lesões encefálicas agudas (3,4%) e outros sintomas leves inespecíficos (11,2%). Conclusões: A maioria das consultas neurológicas em um hospital dedicado à COVID-19 foi solicitada para condições graves que poderiam afetar o desfecho clínico. Os médicos na linha de frente devem ser capazes de reconhecer sintomas neurológicos. Os neurologistas são membros importantes da equipe médica no atendimento hospitalar à COVID-19.

Immunologic follow-up of infants treated with granulocyte transfusion for neonatal sepsis.

The immunologic status and the occurrence of alloimmunization against granulocytes, platelets, lymphocytes, and red cells was evaluated in 33 babies who received granulocyte transfusion because of neonatal sepsis. Nine age-matched babies were examined as control. A first group of 19 infants was examined only once between 6 and 23 months of age. Alloantibodies were searched by the following serologic methods: standard techniques for red cell antibodies; lymphocytotoxicity test; agglutination and immunofluorescence tests on granulocytes and platelets. No antibodies were demonstrated. The immunologic profile was investigated by determining the Ig levels, the percentage of E rosette-forming cells, and the lymphocyte blastic response to phytohemagglutinin and concanavalin A. Granulocyte function was studied by phagocytosis and killing of Candida. No significant differences were observed between treated and control babies. In a second group of 14 infants the occurrence of early immunization within 3 to 9 weeks after the last transfusion was investigated. No evidence of early immunization was found. The present data suggest that following neonatal granulocyte transfusion the risk of adverse immune reactions should be low.

NG methyl-L-arginine increases the hyperthermic effects of prostaglandin E1.

The sympathetic firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and TC) were monitored in urethane-anaesthetized male Sprague-Dawley rats. These variables were measured for a period of 40 min before (baseline values) and 40 min after a 2 mg NG-methyl-L-arginine (NMA) injection plus an intracerebroventricular administration of 500 ng prostaglandin E1 (PGE1) into a lateral cerebral ventricle. No drug was injected in control rats. The results show that NMA enhances the increases in firing rate, TIBAT and TC induced by PGE1. These findings indicate that an inhibitor of nitric oxide synthesis, such as NMA, increases the sympathetic and thermogenic responses to injection of PGE1.

Spatio-temporal interpolation in depth.

Spatio-temporal interpolation creates the impression of motion from a rapid sequence of stationary images by reconstructing the motion path in between the stations actually presented. Thresholds below the diameter of foveal photoreceptors have been obtained with two-dimensional spatio-temporal interpolation. We found that also three-dimensional interpolation, i.e. interpolation in depth, where information from motion detectors tuned to opposite directions in both eyes has to be combined, yields thresholds in the hyperacuity range. The results of parametric experiments favour the interpretation that interpolation occurs at a monocular stage of visual processing, rather than on a stereoscopic stage.

Learning of interpolation in 2 and 3 dimensions.

We investigated learning of spatio-temporal interpolation in depth and its relation to spatio-temporal interpolation in two dimensions by means of a vernier discrimination task. Performance improved with training but improvement did not or only partially transfer between opposite directions of motion in depth. Improvement was also at least partly specific for the eye and for the direction of two-dimensional motion used during monocular training. This specificity might explain the apparent specificity of interpolation in three dimensions. Training with stimuli moving in two dimensions increased performance for a stimulus moving in depth. The results indicate that improvement in spatio-temporal interpolation occurs at least partly on a stage preceding stereoscopic vision, and are a rare example for transfer of improvement between different perceptual tasks.

Vitamin C and nutritional status of institutionalized and noninstitutionalized elderly women in Rome.

A cross-sectional study on 64 institutionalized and 65 noninstitutionalized elderly women has been undertaken. The age range was 60 through 90 years. Vitamin C status was assessed by serum ascorbic acid measurement and the nutritional status was evaluated by a three-day dietary record and main anthropometric measurements. Mean concentration of ascorbic acid was 1.03 mg/dl in the noninstitutionalized and 0.67 mg/dl in the institutionalized group (p less than 0.001). A serum ascorbic acid level less than 0.2 mg/dl was found in one (1.5%) and seven (10.9%) subjects respectively (p less than 0.03). Mean intake of vitamin C was 104.1 mg/d in the former and 87.3 mg/d in the latter group (p = NS), being less than 45 mg/d in 16 living at home and 11 institutionalized women. Serum ascorbic acid level did not correlate significantly to dietary nutrient intake but correlated to activity of daily living level (r = 0.29), vitamin C intake (r = 0.23), ideal body weight (r = -0.15), relative body weight (r = 0.15) and body mass index (r = 0.14). Suggestions are made concerning a higher intake of vitamin C and a more careful catering to improve the health status of the elderly people living in large institutions. The authors also suggest to include the serum ascorbic level determination in the assessment of the general health status of the elderly.

[The use of osteointegrated implants in plastic surgery. Ear reconstruction]. / L'impiego degli impianti osteointegrati in chirurgia plastica. Ricostruzione del padiglione auricolare.

The authors present the case of a 14-year-old patient suffering from first branchial arch syndrome with agenesia of the auricle in which the auricle was reconstructed using osteointegrated implants. The patient had previously undergone numerous attempts at reconstruction using traditional methods, all of which had failed. In order to ensure an accurate preoperative evaluation, the patient was studied using CT with a standard technique and three-dimensional image reconstruction for a qualitative and quantitative evaluation of bone thickness so as to allow the optimal positioning of fixtures. This test also revealed the existence and good degree of development of the middle and internal ear. The Authors then proceeded to implant 4 titanium fixtures into the mastoid process of the temporal bone, three of which were used for fixing the auricle prosthesis and one for the insertion of a bone anchored hearing aid. The epithesis, in soft silicon, was modelled to match the contralateral ear with excellent aesthetic results.

The "one-out, all-out" principle entails the risk of imposing unnecessary restoration costs: a study case in two Mediterranean coastal lakes.

The Water Framework Directive uses the "one-out, all-out" principle in assessing water bodies (i.e., the worst status of the elements used in the assessment determines the final status of the water body). In this study, we assessed the ecological status of two coastal lakes in Italy. Indices for all biological quality elements used in transitional waters from the Italian legislation and other European countries were employed and compared. Based on our analyses, the two lakes require restoration, despite the lush harbor seagrass beds, articulated macrobenthic communities and rich fish fauna. The "one-out, all-out" principle tends to inflate Type I errors, i.e., concludes that a water body is below the "good" status even if the water body actually has a "good" status. This may cause additional restoration costs where they are not necessarily needed. The results from this study strongly support the need for alternative approaches to the "one-out, all-out" principle.

The unresolved fine structure resolved: IRIS observations of the solar transition region.

The heating of the outer solar atmospheric layers, i.e., the transition region and corona, to high temperatures is a long-standing problem in solar (and stellar) physics. Solutions have been hampered by an incomplete understanding of the magnetically controlled structure of these regions. The high spatial and temporal resolution observations with the Interface Region Imaging Spectrograph (IRIS) at the solar limb reveal a plethora of short, low-lying loops or loop segments at transition-region temperatures that vary rapidly, on the time scales of minutes. We argue that the existence of these loops solves a long-standing observational mystery. At the same time, based on comparison with numerical models, this detection sheds light on a critical piece of the coronal heating puzzle.

On the prevalence of small-scale twist in the solar chromosphere and transition region.

The solar chromosphere and transition region (TR) form an interface between the Sun's surface and its hot outer atmosphere. There, most of the nonthermal energy that powers the solar atmosphere is transformed into heat, although the detailed mechanism remains elusive. High-resolution (0.33-arc second) observations with NASA's Interface Region Imaging Spectrograph (IRIS) reveal a chromosphere and TR that are replete with twist or torsional motions on sub-arc second scales, occurring in active regions, quiet Sun regions, and coronal holes alike. We coordinated observations with the Swedish 1-meter Solar Telescope (SST) to quantify these twisting motions and their association with rapid heating to at least TR temperatures. This view of the interface region provides insight into what heats the low solar atmosphere.