Can unsupervised learning methods applied to milk recording big data provide new insights into dairy cow health?

Among the dairy sector's current concerns, the assessment of global animal health status is a complex challenge. Its multidimensionality means that global monitoring tools are rarely considered. Instead, specific disease detection is often studied separately and, due to financial and ethical issues, uses small-scale data sets focusing on few biomarkers. Several studies have already been conducted using milk Fourier transform mid-infrared (FT-MIR) spectroscopy to detect mastitis and lameness or to quantify health-related biomarkers in milk or blood. Those studies are relevant but they focus mainly on one biomarker or disease. To solve this issue and the small-scale data set, in this study, we proposed a holistic approach using big data obtained from milk recording, including milk yield, somatic cell count, and 27 FT-MIR-based predictors related to milk composition and animal health status. Using 740,454 records collected from 114,536 first-parity Holstein cows in southern Belgium, we performed repeated unsupervised learning algorithms based on Ward's agglomerative hierarchical clustering method to find potential interesting patterns. A divide-and-conquer approach was used to overcome the limitation of computational resources in clustering a relatively large data set. Five groups of records were identified. Differences observed in the fourth group suggested a relationship to metabolic disorders. The fifth group seemed to be related to mastitis. In a second step, we performed a partial least squares discriminant analysis (PLS-DA) to predict the probability of belonging to those specific groups for the entire data set. The obtained global accuracy was 0.77 and the balanced accuracy (i.e., the mean between sensitivity and specificity) of discriminating the fourth and fifth groups was 0.88 and 0.96, respectively. Then, a validation of the interpretation of those groups was performed using 204 milk and blood reference records. The predicted probability associated with the metabolic disorders issue had significant correlations of 0.54 with blood ß-hydroxybutyrate, 0.44 with blood nonesterified fatty acids, -0.32 with blood glucose, -0.23 with milk glucose-6-phosphate, and 0.38 with milk isocitrate. In contrast, the predicted probability of belonging to the mastitis group had correlations of 0.69 with milk lactate dehydrogenase, 0.46 with milk N-acetyl-ß-d-glucosaminidase, -0.18 with milk free glucose, and 0.16 with milk glucose-6-phosphate. Consequently, these results suggest that the obtained quantitative traits indirectly reflect some of the main health disorders in dairy farming and could be used to monitor dairy cows on a large scale. By using unsupervised learning on large-scale milk recording data and then validating the pattern using reference laboratory measures, we propose a new approach to quickly assess dairy cow health status.

Identification of chronic stress biomarkers in dairy cows.

Stress in dairy herds can occur from multiple sources. When stress becomes chronic because of a long duration and inability of animals to adapt, it is likely to deeply affect the emotional state, health, immunity, fertility and milk production of cows. While assessing chronic stress in herds would be beneficial, no real consensus has emerged from the literature regarding the indicators of interest. The goal of this study was to compare and evaluate potential biomarkers for chronic stress after inducing stress over a 4-week period through severe overstocking, restricted access to feed and isolated unusual events. A total of 30 cows were involved in the experiment and two similar groups were constituted. Over a 4-week period, the 15 cows of the stress group were housed in overstocked conditions, with 4.6 m2 per cow, including resting and feeding areas. In this area, only seven individual places at the feeding area were available for the 15 cows to generate competition for feed access. Twice during the trial and over a period of 2 h, an additional stress was induced by moving cows to an unfamiliar barn and diffusion of stressing noises (dog barking). Meanwhile, the 15 cows of the control group stayed in the original barn, with more than 10 m2 per cow and more individual places at the feeding area than cow number. On a weekly basis, several variables considered as potential biomarkers for chronic stress were recorded. Collected data were analysed using single trait linear repeated mixed models. No differences were observed regarding milk yield, BW of cows or body condition score but the milk loss was more pronounced in the stress group. The activity was more heterogeneous and the rumination of cows was lower in the stress group. The heart rate was lower in the stress group and showed more heterogeneity at the end of the stress period. No differences were observed regarding salivary cortisol, blood glucose, ß-endorphin, thyroxine and leucocyte profile. A higher level of hair cortisol and blood fructosamine were observed in the stress group at the end of the stress period. Regarding the practical use of the highlighted biomarkers, milk loss may be an effective and easy way to detect general problems, including stress. The blood fructosamine and the hair cortisol concentrations are promising indicators to assess chronic stress in commercial farms.

Practical training of health care providers in insertion of contraceptive implants: findings from two Brazilian centres.

BACKGROUND AND OBJECTIVES: Lack of information and myths or inadequate training of health care providers in the guidance and management of contraceptives could negatively affect choice and eventually continuation rates. Our objectives were to evaluate the impact of clinical and theoretical training of health care professionals on insertion and removal of etonogestrel (ENG)-implant regarding this contraceptive, including pre- and post-training knowledge about insertion and removal techniques, clinical characteristics, side effects and outcomes. MATERIAL AND METHODS: We conducted a cross-sectional study in which a questionnaire was sent to health care providers after they received clinical training in the management of ENG-implant. RESULTS: After training, 78.2% of the 139 participants initiated to offer and inserted up to 5 implants/month and 17.6% between 6 to 10/month. None of the interviewees reported having difficulty with insertions after training, and 87.9% reported feeling very confident for removal. CONCLUSION: Theoretical and practical training appeared important to prepare health care professionals, clarify doubts and promote higher rates of use of contraceptive implants in Brazil, contributing to reduce the rates of unintended pregnancies.

Rummaging through the bin: Modelling marine litter distribution using Artificial Neural Networks.

Marine litter has significant ecological, social and economic impacts, ultimately raising welfare and conservation concerns. Assessing marine litter hotspots or inferring potential areas of accumulation are challenging topics of marine research. Nevertheless, models able to predict the distribution of marine litter on the seabed are still limited. In this work, a set of Artificial Neural Networks were trained to both model the effect of environmental descriptors on litter distribution and estimate the amount of marine litter in the Central Mediterranean Sea. The first goal involved the use of self-organizing maps in order to highlight the importance of environmental descriptors in affecting marine litter density. The second goal was achieved by developing a multilayer perceptron model, which proved to be an efficient method to estimate the regional quantity of seabed marine litter. Results demonstrated that machine learning could be a suitable approach in the assessment of the marine litter issues.

Dietary patterns and body adiposity in children in Brazil: a cross-sectional study.

OBJECTIVES: Many factors are associated with the increase in total and central body adiposity in children, especially eating habits. This has led to an increasing number of studies analysing food patterns, which consider the synergistic effect of food and nutrient intake on the nutritional status. The objective of this study was to identify the dietary patterns of children aged 4-7 years and associate these with different indicators of total and central body adiposity. STUDY DESIGN: Cross-sectional study METHODS: The study consisted of 403 children from a retrospective cohort in Minas Geraes, Brazil. Four indicators of body adiposity were evaluated: body mass index (BMI), waist-to-height ratio (WHtR) and percentages of total and central body fat (assessed by dual-energy X-ray absorptiometry). The dietary habits of the children were evaluated by identifying the dietary patterns using principal component analysis. The adjustment predictor variables were related to the socio-economic characteristics, lifestyle and duration of exclusive breastfeeding. Food patterns were identified by factor analysis. Linear regression was used to estimate the regression coefficient and the confidence interval, considering statistical significance of α = 5%. RESULTS: Five dietary patterns were identified, which explained 42.3% of the data variance: 'Traditional', 'Unhealthy', 'Milk and chocolate', 'Snack' and 'Healthy'. The multiple linear regression model showed that a greater adherence to the 'Traditional' and 'Unhealthy' patterns was related to higher BMI, WHtR, and total and central body adiposity. CONCLUSION: Children with a higher intake of food from the 'Traditional' and 'Unhealthy' patterns showed an increase in total and central body adiposity.

Eosinophilic granulomatosis with polyangiitis and laryngeal involvement: review of the literature and a cross-sectional prospective experience.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis show variable otorhinolaryngological involvement. Up to 14 per cent of granulomatosis with polyangiitis patients have subglottis involvement; little is known about the laryngeal involvement in eosinophilic granulomatosis with polyangiitis. METHOD: A literature review was conducted, together with a prospective cross-sectional analysis of 43 eosinophilic granulomatosis with polyangiitis patients. All patients underwent fibre-optic laryngoscopy with narrow-band imaging, and completed health-related questionnaires. RESULTS: The literature review showed only two cases of laryngeal involvement in eosinophilic granulomatosis with polyangiitis; in our cohort, no cases of subglottis stenosis were found, but local signs of laryngeal inflammation were present in 72 per cent of cases. Of the patients, 16.2 per cent had a pathological Reflux Finding Score (of 7 or higher). CONCLUSION: Laryngeal inflammation in eosinophilic granulomatosis with polyangiitis is frequent. It is possibly due more to local factors than to eosinophilic granulomatosis with polyangiitis itself. However, ENT evaluation is needed to rule out possible subglottis inflammation. These findings are in line with current literature and worthy of confirmation in larger cohorts.

Rehabilitative orbital decompression for Graves' orbitopathy: results of a randomized clinical trial.

PURPOSE: Orbital decompression (OD) is a consolidated procedure for the treatment of exophthalmos in Graves' orbitopathy (GO). The efficacy of the various procedures remains unclear due to the variability of the techniques used. To address this issue, we performed a randomized clinical trial to compare the efficacy of two surgical techniques. The primary endpoint was the reduction in proptosis. Secondary aims were the risk of post-operative diplopia (POD) in primary gaze and other surgical complications. PATIENTS: 38 patients (76 orbits) affected with GO were enrolled and randomized into single lateral decompression (LD) (n = 19) or balanced medial plus lateral wall decompression (MLD) (n = 19). Following surgery, patients were seen for a follow-up ophthalmological evaluation at 6 months. Pre-operative diplopia in secondary gaze was present in 13/38 patients (34.2%, 8/19 treated with LD and 5/19 treated with MLD). RESULTS: The reduction of exophthalmos was greater in patients treated with MLD (5.1 ± 1.5 mm, range 2-8 mm) than in those treated with LD (3.5 ± 1.3 mm, range 1-6.5 mm) (p = 0.01). The overall incidence of POD in primary gaze was 5/38 (13.2%) and all of these patients had pre-operative diplopia in secondary gaze (5/13, 38.5%, vs patients with no pre-operative diplopia p = 0.005). Two of 19 patients (10.5%) treated with LD and 3/19 (15.8%) treated with MLD, developed POD in primary gaze, with no statistical difference between the two techniques. CONCLUSION: MLD provides a better result in terms of proptosis reduction compared to LD. The two techniques used here appear to have a similar safety profile in terms of POD. Pre-operative diplopia in the secondary gaze remains a major risk factor for development of POD.

Sluggish dorsally-driven inhibition of return during orthographic processing in adults with dyslexia.

Dyslexia (D) is a neurodevelopmental reading disorder characterized by phonological and orthographic deficits. Before phonological decoding, reading requires a specialized orthographic system for parallel letter processing that assigns letter identities to different spatial locations. The magnocellular-dorsal (MD) stream rapidly process the spatial location of visual stimuli controlling visuo-spatial attention. To investigate the visuo-spatial attention efficiency during orthographic processing, inhibition of return (IOR) was measured in adults with and without D in a lexical decision task. IOR is the delay in responding to stimuli displayed in a cued location after a long cue-target interval. Only adults with D did not showed IOR effect during letter-string recognition, despite the typical left-hemisphere specialization for word identification. A specific deficit in coherent-dot-motion perception confirmed an MD-stream disorder in adults with D. Our results suggest that adults with D might develop an efficient visual word form area, but a dorsal-attentional dysfunction impairs their reading fluency.

Antioxidant effects of ß-carotene, but not of retinol and vitamin E, in orbital fibroblasts from patients with Graves' orbitopathy (GO).

BACKGROUND: Oxidative stress is involved in the pathogenesis of Graves' orbitopathy (GO) and several antioxidant agents, namely, selenium, quercetin, enalapril, vitamin C, N-acetyl-L-cysteine, and melatonin, have been shown to reduce oxidative stress and its consequences in primary culture of orbital fibroblasts. In addition, selenium is effective for the treatment of mild GO. Here, we investigated the action of three additional antioxidants in orbital fibroblasts, namely, retinol, ß-carotene, and vitamin E. METHODS: Primary cultures of orbital fibroblasts were established from GO patients and control subjects. To induce oxidative stress, cells were treated with H2O2, after which glutathione disulfide (GSSG) (a parameter of oxidative stress), cell proliferation, hyaluronic acid, TNFα, IFNγ, and IL1ß were measured. RESULTS: H2O2-dependent oxidative stress (augmented GSSG) was associated with increased cell proliferation and cytokine release. All the three antioxidant substances reduced GSSG in both GO and control fibroblasts. ß-carotene reduced proliferation in GO, but not in control fibroblasts. IL1ß was reduced by all three substances. Retinol reduced IFNγ in GO and control fibroblasts. CONCLUSIONS: Our study supports an antioxidant role of retinol, ß-carotene, and vitamin E in orbital fibroblasts from patients with GO and provides a basis for a possible clinical use these substances.

Action of three bioavailable antioxidants in orbital fibroblasts from patients with Graves' orbitopathy (GO): a new frontier for GO treatment?

OBJECTIVE: Oxidative stress is involved in the pathogenesis of Graves' orbitopathy (GO) and an antioxidant approach has been advocated for GO treatment. Here, we investigated the action of three antioxidants in orbital fibroblasts, namely, vitamin C, N-acetyl-L-cysteine, and melatonin. METHODS: Primary cultures of orbital fibroblasts from six GO patients and six control subjects were established. Cells were treated with H2O2 to induce oxidative stress. Cell vitality assays were performed to determine the non-cytotoxic dose of each antioxidant. The following assays were performed: glutathione disulfide (GSSG), as a measure of oxidative stress, cell proliferation, hyaluronic acid (HA), TNFα, IFNγ, and IL1ß. RESULTS: H2O2 induced oxidative stress (augmented GSSG), increased cell proliferation as well as cytokine release, but did not affect HA release. All of the three antioxidant substances reduced H2O2-dependent oxidative stress. Vitamin C reduced proliferation in GO, but not in control fibroblasts. N-acetyl-L-cysteine reduced proliferation and IFNγ in GO, and HA and IL1ß in both GO and control fibroblasts. Melatonin reduced IL1ß and HA in GO and control fibroblasts, and IFNγ only in GO fibroblasts. CONCLUSIONS: Our study provides evidence in support of an antioxidant role of vitamin C, N-acetyl-L-cysteine and melatonin in orbital fibroblasts. Some of the effects of these compounds are exclusive to GO fibroblasts, whereas some other are observed also in control fibroblasts. Our observations provide a basis for a possible clinical use of these substances in patients with GO.

Graves' orbitopathy, idiopathic orbital inflammatory pseudotumor and Epstein-Barr virus infection: a serological and molecular study.

OBJECTIVE: One of the hypotheses on the pathogenesis of autoimmune diseases, including Graves' disease (GD) and Graves' orbitopathy (GO), involves bacterial or viral infections. Recently, Epstein-Barr virus (EBV) has been proposed to play a role in the pathogenesis of idiopathic orbital inflammatory pseudotumor (IOIP) in Asians. The aim of the present study was to investigate the possible association of GO with EBV infection/exposure, as compared with IOIP, using serum and tissue samples, as well as primary cultures of orbital fibroblasts. METHODS: Thirty-one patients were studied, including four with IOIP, ten with GO, nine with GD without GO and eight control patients without IOIP, GD and GO. All patients with IOIP and GO underwent orbital decompression. Control patients underwent palpebral surgery. Fibroadipose orbital tissue samples were collected. Serum anti-EBV antibodies were measured in all patients. EBV-DNA was measured in blood samples, orbital tissue samples and primary cultures of orbital fibroblasts. RESULTS: Serum assays showed that the vast majority of patients have had a previous exposure to EBV, but no one had an acute infection. EBV-DNA was detected in ~40% of blood samples from GO, GD and control patients, but in none of the IOIP samples. EBV-DNA was not detected in any of the orbital tissue samples tested or in primary cultures of orbital fibroblasts. CONCLUSIONS: EBV infection does not seem to be associated with GD, GO and IOIP in Caucasians. Whether EBV is involved in IOIP in Asians or other populations remains to be confirmed.

Surgical complications in orbital decompression for Graves' orbitopathy.

The objective of this study is to analyse the complications of orbital decompression in Graves' orbitopathy. The clinical records of 946 patients who had been operated on with orbital decompression for Graves' orbitopathy were reviewed and the intra- and post-operative complications with minimum follow-up of six months were analysed. An extensive review of the literature was carried out to compare results. In the case-series reported here the most frequent complications were: wasting of the temporal region (100%) in patients operated on using a coronal approach; permanent hypoesthesia of V2 (13%) and V1 (8%) in patients operated on with an upper eyelid incision. In only one patient was a total monolateral lesion of V2 reported. The most severe complications consisted in reduction of visual acuity in 5 patients, and CSF leak with cerebral complications in 2 patients, who were operated on with a non-endoscopic endonasal approach. Three patients had intra-operative haemorrhages and 3 patients had post-operative haemorrhages requiring further surgical intervention. The incidence of symptomatic sinusitis/mucoceles was 0.75%. In conclusion, orbital decompression carried out with endoscopic endonasal technique and via transpalpebral accesses appears to be associated with a low incidence of complications. Knowledge of the causes of the possible complications in the different surgical approaches can definitely help to reduce their incidence.

Transorbital endoscopic assisted management of intraorbital lesions: lessons learned from our first 9 cases.

BACKGROUND: The management of intraorbital lesions is challenging and it is strongly dependent to their nature, position and biological behaviour. Traditionally, the superior and lateral compartments of the orbit are addressed via lateral orbitotomy or transcranial approaches. Herein we present our preliminary experience in the management of selected supero-lateral intraorbital lesion through an endoscopic-assisted superior-eyelid approach. METHODOLOGY: All cases of intraorbital lesion treated in two Italian tertiary care referral centres using a superior eyelid endoscopic-assisted transorbital approach were retrospectively reviewed. RESULTS: Nine patients have been analysed. The aim of surgery was diagnostic in 5 cases and curative in the remaining 4 patients. Significant tissue biopsy was obtained in all the five diagnostic procedures. Complete resection was obtained in 3/4 lesions. No major intra- or postoperative complications have been observed. Mean surgical time was 68 minutes. Mean hospitalization time was 4.4 days. All patients were satisfied about the surgical procedure, as emerged by the post-operative counselling. At present, the mean follow-up time is 18 months, ranging from 11 to 25 months. CONCLUSIONS: Our preliminary results are promising with successful functional and cosmetic outcomes and reduced morbidity for the patient. This approach should be considered as an option for selected intraorbital lesions.

How does radiotherapy impact swallowing function in nasopharynx and oropharynx cancer? Short-term results of a prospective study.

The objective of this study is to report the initial results of a prospective trial assessing instrumental deglutition function in nasopharynx and oropharynx cancers after radio or chemoradiotherapy using intensity-modulated radiotherapy (IMRT). IMRT was delivered aiming to spare the swallowing organ at risk (SWOARs) for Stage II-IV naso- and oropharynx cancer. Objective instrumental assessment included videofluoroscopy (VFS), fiberoptic endoscopic evaluation of swallowing (FEES) and oro-pharyngeal-oesophageal scintigraphy (OPES) at baseline and at 1 month after radiotherapy. Dysphagia parameter scores were calculated at each exam after liquid (L) and semi-liquid (SL) bolus intake: pre-deglutition penetration, aspiration, pharyngeal transit time (PTT) and hypopharyngeal retention index (HPRI). Overall, 20 patients (6 nasophaynx and 14 oropharynx) completed treatment and instrumental assessment after 1 month. Comparison between pre- and post-treatment HPRI score values showed a significant worsening in both FEES-L (p = 0.021) and SL (p = 0.02) and at VFS-L (p = 0.008) and SL (p = 0.005). Moreover, a relationship between HPRI worsening at FEES-L and FEES-SL (p = 0.005) as well as at VFS-L and VFS-SL (p < 0.001) was observed. PTT was not significantly affected by radiotherapy (p > 0.2). Only a few patients experienced pre-deglutition penetration (1 patient with base of tongue cancer at FEES-L and SL) and aspiration (1 patient with nasopharynx cancer at OPES-L and FEES-SL) after radiotherapy. Our early results showed that IMRT-SWOARs sparing caused a significant increase in the post-deglutition HPRI score. Longer follow-up will be necessary to evaluate if the increase of HPRI is related to a high risk of developing late aspiration.

Isolated laryngeal leishmaniasis in an immunocompetent patient: a case report.

Isolated laryngeal leishmaniasis in an immunocompetent patient: a case report. OBJECTIVE: Isolated laryngeal Leishmaniasis presents neither explicit laryngeal lesions nor specific symptoms. In fact, it may mimic many inflammatory and neoplastic diseases. Considering the low incidence of this atypical localization, laryngeal Leishmaniasis, is rarely contemplated by physicians in differential diagnoses of laryngeal tumour lesions. We present the case of a 62-year-old immunocompetent subject who developed a single Leishmania mucosal lesion on the left vocal cord, simulating a laryngeal cancer. METHODS: A case report and discussion of the clinical case by referring to the literature. RESULTS: Specific therapy with miltefosine led to clinical and endoscopic improvement. We had no relapse after three years of follow-up. CONCLUSIONS: This clinical case highlights the need to consider isolated laryngeal Leishmaniasis in the differential diagnoses of laryngeal tumour lesions, even in immunocompetent subjects who live in endemic zones, in order to ensure an early and correct therapeutic approach.

Vertigo in childhood: proposal for a diagnostic algorithm based upon clinical experience.

The aim of this paper is to analyse, after clinical experience with a series of patients with established diagnoses and review of the literature, all relevant anamnestic features in order to build a simple diagnostic algorithm for vertigo in childhood. This study is a retrospective chart review. A series of 37 children underwent complete clinical and instrumental vestibular examination. Only neurological disorders or genetic diseases represented exclusion criteria. All diagnoses were reviewed after applying the most recent diagnostic guidelines. In our experience, the most common aetiology for dizziness is vestibular migraine (38%), followed by acute labyrinthitis/neuritis (16%) and somatoform vertigo (16%). Benign paroxysmal vertigo was diagnosed in 4 patients (11%) and paroxysmal torticollis was diagnosed in a 1-year-old child. In 8% (3 patients) of cases, the dizziness had a post-traumatic origin: 1 canalolithiasis of the posterior semicircular canal and 2 labyrinthine concussions, respectively. Menière's disease was diagnosed in 2 cases. A bilateral vestibular failure of unknown origin caused chronic dizziness in 1 patient. In conclusion, this algorithm could represent a good tool for guiding clinical suspicion to correct diagnostic assessment in dizzy children where no neurological findings are detectable. The algorithm has just a few simple steps, based mainly on two aspects to be investigated early: temporal features of vertigo and presence of hearing impairment. A different algorithm has been proposed for cases in which a traumatic origin is suspected.

Benign tumours affecting the deep lobe of the parotid gland: how to select the optimal surgical approach.

Many types of approaches allow extra-capsular dissection in the deep parotid parenchyma in the treatment of benign tumours. A transcervical approach (TCA), transparotid approach (TPA) and a combined transcervical-transparotid approach (TPTCA) are the three main procedures performed to expose the deep parenchyma. We conducted a retrospective chart review enrolling 24 consecutive patients treated for benign tumours affecting the deep lobe of the parotid. Review of the surgical data was accompanied by careful follow-up to establish surgical morbidity, functional (Frey's Syndrome and first-bite syndrome) and aesthetical outcomes. A TPA was performed in the majority of cases; in 26% superficial parotidectomy was not required (selective deep parotidectomy). Minor's test showed a low rate of Frey's syndrome (3 cases of 23, 13%). No long-lasting first-bite syndrome was reported. Some additional procedures were easily performed in order to improve aesthetical results (rotational flap of sternocleidomastoid muscle, free abdominal fat transfer); these had the same results as selective deep parotidectomy. TCA (or TPTCA) ensures the best control of the facial nerve, providing good exposure and good functional and aesthetical results (without sparing the superficial parenchyma if additional techniques are performed with the aim of reducing skin depression in the treated area). The choice of the approach should have only the aim of safe resection and should not be influenced by aesthetical outcome; the craniocaudal level of the tumour seems to be the best indicator of the feasibility of the procedure also considering the branches of the facial nerve. In our experience, mandibulotomy can always be avoided.

Prophylactic central compartment lymph node dissection in papillary thyroid carcinoma: clinical implications derived from the first prospective randomized controlled single institution study.

BACKGROUND: The benefits of prophylactic central compartment lymph node dissection (pCCND) in papillary thyroid cancer (PTC) are still under investigation. This treatment seems to reduce PTC recurrence/mortality rates but has a higher risk of surgical complications. The lack of prospective randomized trials does not allow definitive recommendations. The aim of this prospective randomized controlled study was to evaluate the clinical advantages and disadvantages of pCCND. PATIENTS: A total of 181 patients with PTC without evidence of preoperative/intraoperative lymph node metastases (cN0) were randomly assigned to either Group A (n = 88) and treated with total thyroidectomy (TTx) or Group B (n = 93) and treated with TTx + pCCND. RESULTS: After 5 years of followup, no difference was observed in the outcome of the two groups. However, a higher percentage of Group A were treated with a higher number of (131)I courses (P = .002), whereas a higher prevalence of permanent hypoparathyroidism was observed in Group B (P = .02). No preoperative predictors of central compartment lymph node metastases (N1a) were identified. Only three patients were upstaged, and the therapeutic strategy changed in only one case. CONCLUSIONS: cN0 patients with PTC treated either with TTx or TTx + pCCND showed a similar outcome. One advantage of TTx + pCCND was a reduced necessity to repeat (131)I treatments, but the disadvantage was a higher prevalence of permanent hypoparathyroidism. Almost 50% of patients with PTC had micrometastatic lymph nodes in the central compartment, but none of the presurgical features analyzed, including BRAF mutation, was able to predict their presence; moreover, to be aware of their presence does not seem to have any effect on the outcome.

Effect of intracervical anesthesia on pain associated with the insertion of the levonorgestrel-releasing intrauterine system in women without previous vaginal delivery: a RCT.

STUDY QUESTION: Is the pain associated with levonorgestrel-releasing intrauterine system (LNG-IUS) insertion reduced by intracervical anesthesia in women without previous vaginal birth? SUMMARY ANSWER: Intracervical anesthesia was not associated with reduced pain in women without previous vaginal birth. WHAT IS KNOWN ALREADY: The pain associated with the insertion of intrauterine contraceptives (IUCs) is a limiting factor for the use of these contraceptives by some women. No prophylactic pharmacological intervention has proven efficacy in relieving pain during or after the insertion of IUCs. However, previous studies included women with previous vaginal delivery, and injectable intracervical anesthesia was not evaluated in any of these studies. STUDY DESIGN, SIZE, DURATION: This was a randomized, open, parallel-group clinical trial that evaluated 100 women without previous vaginal delivery who wished to use the LNG-IUS for the first time. These women were evaluated immediately after LNG-IUS insertion and then 2 h and 6 h later. PARTICIPANTS/MATERIALS, SETTING, METHODS: The 100 women were randomized into two groups: (i) use of a non-steroidal anti-inflammatory drug (NSAID) (ibuprofen, 400 mg) 1 h prior to LNG-IUS insertion; or (ii) 2% lidocaine intracervical injection 5 min prior to LNG-IUS insertion. The women were evaluated immediately after LNG-IUS insertion and then 2 h and 6 h after insertion. Two pain scales were used (the visual analogue scale and the facial pain scale) in addition to assessing the ease of insertion (as rated by the provider) and the level of discomfort during the procedure (as rated by the patient). Multivariate logistic regression was performed to analyze the predictors associated with moderate/severe pain. MAIN RESULTS AND THE ROLE OF CHANCE: The pain and discomfort associated with LNG-IUS insertion, and the ease of insertion of the LNG-IUS did not differ between the groups. Nulliparity was more associated with moderate/severe pain [adjusted odds ratio (OR): 3.1 (95% confidence interval (CI): 1.3-7.80]. Injectable intracervical anesthesia use reduced the risk of moderate/severe pain by 40% [adjusted OR: 0.6 (95% CI: 0.2-1.4)]. The difference between the mean pain score in the intracervical anesthesia group and the NSAID group was <10%; thus, the effect size of the intervention was not significant. LIMITATIONS, REASONS FOR CAUTION: Intracervical anesthesia was compared with an oral medication in this study. Intracervical injection of a saline solution or even a dry needling as the placebo for a double-blind study could be a more adequate control; however, this approach was not a protocol approved by the institutional review board. Considering that the majority of the insertions were easy (>80% in both groups), the results may not be extrapolated to difficult insertions with moderate/severe pain where local anesthesia may have a role. WIDER IMPLICATIONS OF THE FINDINGS: The findings can be generalized to most insertions in nulliparous women or in those without a previous vaginal delivery. There is currently no evidence to recommend the routine use of prophylactic intracervical anesthesia prior to LNG-IUS insertion; there is no evidence that this treatment reduces insertion-related pain. STUDY FUNDING/COMPETING INTERESTS: RAF and CSV give occasional lectures for Bayer Healthcare. This study received funding from the National Institute of Hormones and Women's Health, National Council for Scientific and Technological Development (CNPq). TRIAL REGISTRATION NUMBER: NCT02155166.

Long-term follow up of sudden sensorineural hearing loss patients treated with intratympanic steroids: audiological and quality of life evaluation.

OBJECTIVE: To evaluate the long-term stability of intratympanic steroids and investigate the 'real' impact of sudden sensorineural hearing loss on patients. METHOD: A total of 14 patients treated with intratympanic steroids were evaluated by audiometric and vestibular examinations. The modified Glasgow Benefit Inventory was used to evaluate quality of life changes after intratympanic steroid treatment. RESULTS: There was no significant difference between pure tone average post-intratympanic steroids and at follow up. The general Glasgow Benefit Inventory score was not significantly associated with the presence of tinnitus or dizziness, or with patient age. The change in pure tone average after intratympanic steroid treatment did not correlate with social or physical scores, but correlated strongly with the general Glasgow Benefit Inventory score (p = 0.0023). Intratympanic steroid administration led to a stable improvement in hearing. Quality of life assessment showed that patients can feel satisfaction regardless of the hearing outcome. Patients who regained a social hearing level expressed greater satisfaction than patients without serviceable hearing. Overall, quality of life improvement was not related to hearing improvement. CONCLUSION: Sudden sensorineural hearing loss is devastating. Considering the audiological effects alone ignores the 'human' perspective. Audiological success can correlate with poor quality of life outcome.