The occlusal imaging and analysis system by T-scan III in tinnitus patients.

BACKGROUND: Several studies have demonstrated that the prevalence of temporomandibular disorders (TMDs) in tinnitus patients ranges from 7% to 95%, and it is reported in literature that idiopathic tinnitus patients should be referred to a dentist to define whether or not the tinnitus is associated with TMD. However, the possible pathophysiological relation between TMDs and tinnitus is not generally investigated in clinical practice. METHODS: The patterns and forces of occlusal contacts have been studied by means of T-scan III in 47 tinnitus patients (23 suffering from idiopathic tinnitus and 24 affected by Ménière disease [MD]) and 13 healthy subjects. RESULTS: The center of force target was offset in the opposite direction in 15/23 idiopathic tinnitus and in 7/24 MD patients (p = 0.026). No significant variation was found in the occlusal force. CONCLUSIONS: Our data suggest that a diagnostic screening method for occlusal stability in the intercuspidal position might be clinically useful in idiopathic tinnitus patients.

Endoscopic Adenoidectomy in Children With Otitis Media With Effusion and Mild Hearing Loss.

OBJECTIVES: Surgical management of children with chronic otitis media with effusion (OME) includes tympanostomy tube insertion or adenoidectomy, alone or with myringotomy and tube insertion. The aim of this study was to compare the effectiveness of transoral microdebrider endoscopic-assisted adenoidectomy (TOMEA) and traditional adenoidectomy in the management of children with mild hearing loss due to OME and chronic adenoiditis. METHODS: This prospective, double-blind and controlled study involved 120 consecutive patients aged 4-12 years, who were randomised 1:1 to undergo TOMEA or traditional adenoidectomy under general anesthesia. All the patients underwent a complete otolaryngological examination, including nasopharyngeal fibre endoscopy (NFE), pneumatic otoscopy, otomicroscopy, tympanometry and supraliminar tonal audiometry, upon enrolment, and three and nine months postoperatively. RESULTS: There were no statistically significant differences in age or gender distribution between the TOMEA group (mean age, 4.9±1.1 years; 53.3% males) and the traditional adenoidectomy group (mean age, 5.3±0.9 years; 56.7% males). Both procedures led to a significant improvement in choanal patency (P<0.01) and all of the otological and audiological parameters (P<0.01) 3 and 9 months postoperatively, although postoperative NFE showed that the mean percentage of residual choanal obstruction was significantly less in the TOMEA group (P=0.02). There was no significant between-group difference in the percentage of children with tympanic membrane changes, but the postoperative prevalence of children with a type B tympanogram was significantly lower in the TOMEA group after 3 (15.0% vs. 31.7%, P=0.05) and 9 months (18.3% vs. 38.3%, P=0.02), as was the percentage of children with mild conductive hearing loss (3.3% vs. 23.3%, P<0.01; and 8.3% vs. 28.3%, P<0.01). CONCLUSION: Although both TOMEA and traditional adenoidectomy are effective in treating children with mild hearing loss due to adenoidal hypertrophy and OME, the former achieves the greater reduction in residual adenoidal hypertrophy and better audiological outcomes.

Determinants of venom-specific IgE antibody concentration during long-term wasp venom immunotherapy.

BACKGROUND: Venom immunotherapy (VIT) is an effective treatment for subjects with systemic allergic reactions (SR) to Hymenoptera stings, however there are few studies concerning the relevance of the venom specific IgE changes to decide about VIT cessation. We assessed IgE changes during a 5-year VIT, in patients stung and protected within the first 3 years (SP 0-3) or in the last 2 years (SP 3-5), and in patients not stung (NoS), to evaluate possible correlations between IgE changes and clinical protection. METHODS: Yellow jacket venom (YJV)-allergic patients who completed 5 years of VIT were retrospectively evaluated. Baseline IgE levels and after the 3rd and the 5th year of VIT were determined; all patients were asked about field stings and SRs. RESULTS: A total of 232 YJV-allergic patients were included and divided into the following groups: 84 NoS, 72 SP 0-3 and 76 SP 3-5. IgE levels decreased during VIT compared to baseline values (χ(2) = 346.029, p < 0.001). Recent vespid stings accounted for significantly higher IgE levels despite clinical protection. IgE levels after 5 years of VIT correlated significantly with Mueller grade (F = 2.778, p = 0.012) and age (F = 6.672, p = 0.002). During follow-up from 1 to 10 years after VIT discontinuation, 35.2 % of the contacted patients reported at least one field sting without SR. CONCLUSIONS: The yellow jacket-VIT temporal stopping criterion of 5 years duration did not result in undetectable IgE levels, despite a long-lasting protection. A mean IgE decrease from 58 to 70 % was observed, and it was less marked in elderly patients or in subjects with higher Mueller grade SR.

Reliability of postural control measures in children and young adolescents.

Although many studies have been carried out regarding postural stability during pediatric age, reliable information and a complete analysis of all age groups are still lacking. The purpose of this study was to verify the test-retest reliability of posturographic parameters in four sensory conditions and provide normative values for children and young adolescents. 289 subjects, aged 6-14 years, were assessed by means of the static posturography system SVeP. 173 elementary school pupils (114 males and 59 females, aged 6-10 years; mean age 8.80 ± 1.53) and 116 middle school students (60 males and 56 females, aged 11-14 years; mean age 12.6 ± 0.9) underwent static posturography in two consecutive trials with four testing conditions: eyes open and eyes closed with and without foam pads. The participants were divided into nine age groups. Thirty healthy young adults were also recruited for comparison. The analysis of test-retest reliability demonstrated an excellent reliability of velocity measurement and a moderate reliability of area measurement. Velocity and area decreased significantly with age in all sensory conditions, indicating an improvement in postural control from childhood to adolescence. Postural stability had not reached the adult level by the age of 13-14 years. Reliable information regarding postural stability can be obtained in children and young adolescents by means of stabilometric parameters. These data can be used as a reference for early detection of atypical postural development and for the assessment of dizziness and balance disorders in children.

Validation of the Italian Voice Handicap Index-10.

OBJECTIVE: Time consuming is an important aspect in assessing dysphonic patients. So, the English version of the Voice Handicap Index (VHI-30), a self-administered questionnaire consisting of 30 items used to evaluate patients' self-perception of voice problems, was reduced to 10 items (VHI-10) for clinical purposes. In 2010, an Italian version of VHI-30 was validated, now the aims of this study were to analyze the psychometric properties of an Italian version of VHI-10 and to evaluate its validity in a cohort of patients affected by organic or functional dysphonia. STUDY DESIGN: Cross-sectional study. METHODS: The Italian version of the VHI-30 was submitted to 372 dysphonic participants and 120 healthy control subjects and was conducted again 2 weeks later. The 10 items constituting the VHI-10 were extracted from the VHI-30. For 73 dysphonic patients, the questionnaire was also administered after treatment. RESULTS: The scores of the control group were significantly lower with respect to all diagnostic subgroups (P<0.001). The Cronbach's α, test-retest, and Pearson's correlation index demonstrated high reliability and validity of the Italian VHI-10. The ratio of the VHI-10 and VHI-30 scores was higher than 0.333 in all subgroups. CONCLUSION: This study demonstrated that the Italian VHI-10 is a robust tool that can adequately represent and replace the VHI-30. The reported results support the use of the VHI-10 for the Italian population in clinical settings owing to its validity and rapid and simple use.

Validation of the Italian version of the singing voice handicap index.

Singers constitute a specific population that is particularly sensitive to vocal disability, which may have a higher impact on their quality of life compared to non-singers. A specific questionnaire, the Singing Voice Handicap Index (SVHI), was created and validated aimed to measure the physical, social, emotional and economic impacts of voice problems on the lives of singers. The aim of this study was to validate the Italian version of the SVHI. The validated English version of the SVHI was translated into Italian and then discussed with several voice care professionals. The Italian version of the SVHI was administered to 214 consecutive singers (91 males and 123 females, mean age: 32.62 ± 10.85). Voice problem complaints were expressed by 97 of the singers, while 117 were healthy and had no voice conditions. All subjects underwent a phoniatric consultation with videolaryngostroboscopy to ascertain the condition of the vocal folds. Internal consistency of the Italian version of the SVHI showed a Cronbach's α of 0.97. The test-retest reliability was assessed by comparing the responses obtained by all subjects in two different administrations of the questionnaire; the difference was not significant (p = ns). The SVHI scores in healthy singers was significantly lower than the one obtained in the group of singers with a vocal fold abnormality (29.26 ± 25.72 and 45.62 ± 27.95, p < 0.001, respectively). The Italian version of the SVHI was successfully validated as an instrument with proper internal consistency and reliability. It is a suitable instrument for the self-evaluation of handicaps related to voice problems in the context of singing.

Bone disease in adult patients with ß-thalassaemia major: a case-control study.

Despite the extraordinary improvements carried out in diagnostic and therapeutic management of thalassaemia major over the past few decades, bone demineralization is still a common finding, even in optimally treated patients. The relationships between bone density and several clinical characteristics or hematological markers have been described, and many factors contributing to demineralization have been identified; among them endocrine complications seem to play an important role. Nevertheless, the complex etiological mechanisms of this heterogeneous osteopathy still remains incompletely clarified. While previous studies focused on the characteristics of thalassaemic patients affected from bone demineralization, we conducted a case-control study focused on thalassaemic patients free from bone disease, aimed to detect the distinctive characteristics and any possible protective feature. Among a large cohort of 150 adult patients with ß-thalassaemia major, we enrolled 20 patients with normal bone mineralization and 20 patients with osteoporosis matched for gender, BMI, age at first transfusion, serum ferritin and pre-transfusional hemoglobin (Hb) levels. The differences in demographic, clinical and endocrinological profiles were investigated, correcting for physical and hematological features known as confounding variables. The comparison of the two groups for biochemical parameters and endocrine function showed a protective role of normal gonadic function and IGF-1 levels against osteoporosis, and a similar influence of hypoparathyroidism. Treatment-corrected hypothyroidism and diabetes seemed not to affect bone mineralization. In conclusion, from a different perspective our results corroborate the role of endocrinopathies in thalassaemic osteopathy, and once again underline the crucial importance of an early and multi-disciplinary intervention in preventing bone complications in thalassaemic patients.

Ambulatory phonation monitoring in a sample of 92 call center operators.

OBJECTIVES: The voice is a primary work tool for call center operators, but the main risk factors for voice disorders in this category have not yet been clarified. This study aimed to analyze the vocal behavior in call center operators and search for correlations between the daily voice dose and the self-perceived voice-related handicap. STUDY DESIGN: Prospective. SUBJECTS AND METHODS: Ninety-two call center operators (aged 24-50 years) underwent ambulatory phonation monitoring during a working day and were administered the Voice Handicap Index (VHI) questionnaire and a questionnaire concerning smoking habits, symptoms, and extrawork activities requiring intensive voice use. RESULTS: Mean percentage phonation time (PT) during work was 14.74% and ranged from 4% to 31%. There was a significant difference between the percentage PT in working time and in extrawork time; however, subjects with high percentage PT in working time maintained a high value also in extrawork time. The mean PT was 87.5 ± 35.8 minutes and was not correlated with age, gender, number of work hours, symptoms, extraprofessional voice use, and VHI scores. The mean amplitude was significantly higher in subjects with longer PT and higher pitch (P < 0.001). VHI score (median = 9) was slightly higher than in the general population but not related to the number of work hours, indicating that work time was not a critical factor in causing the perception of voice problems. CONCLUSION: Our study provides data about the voice behavior of a large cohort of call center operators and demonstrates that the number of work hours and the percentage PT are not statistically related to the perception of voice disturbances in this working category.

Audiological follow-up of 24 patients affected by Williams syndrome.

Williams syndrome is a neurodevelopmental disorder associated with cardiovascular problems, facial abnormalities and several behavioural and neurological disabilities. It is also characterized by some typical audiological features including abnormal sensitivity to sounds, cochlear impairment related to the outer hair cells of the basal turn of the cochlea, and sensorineural or mixed hearing loss, predominantly in the high frequency range. The aim of this report is to describe a follow-up study of auditory function in a cohort of children affected by this syndrome. 24 patients, aged 5-14 years, were tested by means of air/bone conduction pure-tone audiometry, immittance test and transient evoked otoacoustic emissions. They were evaluated again 5 years after the first assessment, and 10 of them underwent a second follow-up examination after a further 5 years. The audiometric results showed hearing loss, defined by a pure tone average >15 dB HL, in 12.5% of the participants. The incidence of hearing loss did not change over the 5-year period and increased to 30% in the patients who underwent the 10-year follow-up. Progressive sensorineural hearing loss was detected in 20% of the patients. A remarkable finding of our study regarded sensorineural hearing impairment in the high frequency range, which increased significantly from 25% to 50% of the participants over the 5-year period. The increase became even more significant in the group of patients who underwent the 10-year follow-up, by which time the majority of them (80%) had developed sensorineural hearing loss. Otoacoustic emissions were found to be absent in a high percentage of patients, thus confirming the cochlear fragility of individuals with Williams syndrome. Our study verified that most of the young Williams syndrome patients had normal hearing sensitivity within the low-middle frequency range, but showed a weakness regarding the high frequencies, the threshold of which worsened significantly over time in most patients.

Public awareness of ear and hearing management as measured using a specific questionnaire.

Public awareness of audiological issues has never been measured in the general public even if the World Health Organization (WHO) has detected a common urgent need for action to prevent and manage ear diseases and hearing loss. The aim of this study was to measure urban community citizens' awareness of managing and preventing ear disease and hearing loss using a specific questionnaire. A questionnaire was formulated on the basis of WHO material concerning the major specific audiological issues and attitudes, focusing in particular on four domains: (1) knowledge of infant hearing loss, (2) correct management of the ears including cleaning and treating, (3) focus on the effect of overexposure to loud sounds and noise, (4) underestimated ear symptoms leading to diagnostic delay. 254 volunteers were enrolled in this cross-sectional study by a team of medical doctors and audiologists stationed in a mobile unit that visited different areas of Milan, Italy. More than 80% of correct responses were given to almost all of the statements by the interviewees, although certain important knowledge was found to be lacking. The proposed audiological questionnaire seems to be a suitable tool to evaluate the public awareness of ear and hearing management. The results showed a need for continued development of comprehensive hearing conservation programs, focused on hearing aid management and early infant hearing loss identification as well as noise exposure.

Balance function in patients with Williams syndrome.

Impaired control of balance has been described in Williams syndrome (WS). The aim of this study was to investigate balance function by means of clinical and instrumental tests in order to measure postural sway in people with WS in an objective way. 23 WS patients (11 males, 12 females, mean age 17.52 ± 8.33 years) and 23 healthy subjects (11 males, 12 females, mean age 17.74 ± 8.93 years) performed static posturography with eyes open and closed, on a firm surface and on foam pads. The WS patients had higher mean length, velocity and surface values than controls under all of the test conditions, and their length and surface values were significantly higher in the eyes open test. The cognitive abilities of the WS patients were not related to their stabilometric performance. The greatest differences between the WS patients and the controls were found mainly in the older subjects. WS patients are more unstable than healthy subjects of the same age, particularly when they use visual information to maintain their balance: i.e. under conditions of normal everyday life. Possible explanations may be the ophthalmologic problems and the visuospatial difficulties attributed to a neural processing abnormality involving the dorsal stream impairment model. The balance function of WS patients is different from that of normal developing subjects, especially after adolescence when postural control is generally complete. This suggests an atypical developmental trajectory.

Auditory late potentials in normal-hearing adult subjects with Down's syndrome.

OBJECTIVE: Several studies have demonstrated that adult subjects with Down's syndrome (DS) and hearing impairments show significantly delayed latencies in auditory late potentials (ALPs). The aim of this study was to investigate whether the differences were still present in ALPs in an adult DS population with normal hearing, taking into consideration sex, handedness, and head size. STUDY DESIGN: Prospective study. SETTING: Audiology unit of the hospital Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. PATIENTS: Sixteen normal-hearing adult DS subjects referred to the health monitoring program for DS patients of Vivi Down Onlus Association in Milan, Italy (7 male subjects with a mean age of 26 ± 7.74 yr and 9 female subjects with a mean age of 28 ± 8.63 yr) and 16 controls (7 male subjects with a mean age of 26 ± 7.74 yr and 9 female subjects with a mean age of 28 ± 8.86 yr) matched for sex, age, and handedness. MAIN OUTCOME MEASURE: The 2 negative peaks, N1 and N2, and the 2 positive peaks, P1 and P2, of ALP. RESULTS: ALP N1 and P2 components were well defined in all subjects. The P1 and N2 components were less evident than the others. There were significant delayed latencies in the DS group with respect to the control subjects for P1, N1, P2, and N2 components. CONCLUSION: Our study demonstrated that ALP longer latencies are present in adult DS participants even when they have a normal hearing threshold, regardless of handedness and head size.

VTMR, a new speech audiometry test with verbal tasks and motor responses.

OBJECTIVES: The aim of this study was to design a complementary speech audiometry test using verbal tasks and motor responses (VTMR) to assess the ability of a subject to understand and perform simple motor tasks with 3-dimensional objects, to describe its construction, and to show the preliminary results of a pilot study on the Italian version of the test. METHODS: The items used in the test setting included 1 base, 1 hammer, 1 wooden structure with 4 sticks, and 5 rings of different colors and 20 lists with 5 verbal tasks per list. The VTMR test and bisyllabic speech audiometry were evaluated in normal-hearing subjects with and without cognitive impairment and in subjects with sensorineural hearing loss. RESULTS: All normal-hearing subjects without cognitive impairment performed the VTMR tasks (100%) correctly at 35 dB sound pressure level. In subjects with sensorineural hearing loss, the percentage of correct answers was significantly higher for the VTMR test than for bisyllabic speech audiometry above 50 dB sound pressure level. This percentage was higher for the VTMR also in normal-hearing subjects with poor cognitive skills. CONCLUSIONS: The VTMR might make it easier to check patients' ability to understand verbal commands than does traditional speech audiometry, in particular in those patients with poor test-taking skills.

Audiological findings in Williams syndrome: a study of 69 patients.

The aim of this study was to investigate, in a clinical setting, the auditory function of a group of individuals affected by Williams syndrome (WS). Sixty-nine patients with WS, aged 2-30, underwent comprehensive audiological testing including air/bone conduction behavioral audiometry, speech audiometry, tympanometry and measurement of the acoustic reflex, transient evoked otoacoustic emissions and brainstem auditory evoked responses. Hearing loss, defined by a pure-tone average above 15 dB HL, affected 22.6% of the patients studied with traditional audiometry and was mostly slight in severity. Hearing loss was conductive in 9.4% of patients, mainly children with otitis media with effusion, and sensorineural in 13.2% of patients. However, 30% of the ears studied had a hearing impairment in the high frequency range (high-frequency pure-tone audiometry above 15 dB HL), higher in participants above 15 years (46.15%) than in the younger ones (23.45%). Contralateral stapedial reflexes were present in all patients with A-type tympanograms. Transient otoacoustic emissions were absent in 44% of the ears of patients with normal hearing. Brainstem auditory evoked responses fell within normal ranges thus confirming the absence of retrocochlear dysfunction. Although hearing loss does not seem to be frequent, a cochlear fragility, especially in the high frequency range, related to outer hair cells is characteristic of WS. Therefore we strongly recommend monitoring patients affected by WS using annual audiometric tests and performing otoacoustic emissions in order to identify a subclinical cochlear dysfunction which might benefit from an audiological follow up before the possible onset of hearing loss.

Narrowband ultraviolet B phototherapy in childhood vitiligo: evaluation of results in 28 patients.

Phototherapy using narrowband ultraviolet B (UVB) is considered among the treatments of choice in vitiligo, even in childhood. The objective of the current study was to evaluate the profile of safety and effectiveness of such therapy in a group of children. An open, uncontrolled study was performed on 28 children with vitiligo who were receiving narrow band UVB phototherapy. The children were classified according to vitiligo type and phototype. Family history and presence of thyroid disease were investigated. Eighteen patients had received other treatments that was stopped 3 months before starting phototherapy. Phototherapy was administered twice a week. The mean duration of therapy was 10 ± 3.4 months. The mean total dose administered was 156.12 ± 79.4 J/cm(2). Photographs of lesions were taken before and at the end of treatment. The response to phototherapy was expressed as percentage of repigmentation. The data were statistically analyzed using SPSS (SPSS Inc., Chicago, IL). Fourteen percent of patients showed excellent response, 28.6% good response, 25% moderate response, and 28.6% mild response; the remaining 3.5% were not responsive. No side effects were observed except mild erythema requiring a decrease in dosage in a few patients. The results of the present study confirm those of other authors, with better results than adults probably related to good adherence of patients and their families. Nevertheless, high cumulative doses are not necessarily related to a good response. Therefore, we suggest stopping treatment after 6 months in nonresponding cases.

Comparing postoperative quality of life in children after microdebrider intracapsular tonsillotomy and tonsillectomy.

OBJECTIVE: To evaluate postoperative quality of life in patients undergoing microdebrider intracapsular tonsillotomy and adenoidectomy (PITA) in comparison with traditional adenotonsillectomy (AT) and to assess PITA's efficacy in solving upper-airway obstructive symptoms. METHODS: 29 children with adenotonsillar hyperplasia referred for AT were included. Patients were divided into two groups: Group 1 (underwent PITA) included 14 children (age 5.1±1.8 years) affected by night-time airway obstruction without a relevant history of recurrent tonsillitis; Group 2 (underwent AT) included 15 children (age 5.2±1.7 years) with a history of upper-airway obstruction during sleep and recurrent acute tonsillitis. Outcomes measures included the number of administered pain medications, time before returning to a full diet, Obstructive Sleep Apnea survey (OSA-18), parent's postoperative pain measure questionnaire (PPPM) and Wong-Baker Faces Pain Rating Scale (WBFPRS). RESULTS: Postoperative pain was significantly lower in the PITA group, as demonstrated by PPPM and WBFPRS scores and by a lower number of pain medications used. PITA group also resumed a regular diet earlier (P<0.001). OSA-18 scores proved that both PITA and AT were equally effective in curing upper-airway obstructive symptoms. CONCLUSION: PITA reduces post-tonsil ablation morbidity and can be a valid alternative to AT for treating upper-airway obstruction due to adenotonsillar hyperplasia.

Neurofeedback for subjective tinnitus patients.

OBJECTIVE: Previous studies report that enhanced power in the delta range (1.5-4Hz) and reduced power in the alpha frequency band (8-12Hz) were most pronounced in the temporal regions. These studies referred to the 8-12Hz activity as tau activity, and they created a new neurofeedback protocol to treat tinnitus using a temporally generated tau rhythm (8-12Hz) and slow waves in the delta range (3-4Hz) for feedback. This study aims to repeat this protocol and to evaluate its effect on tinnitus. METHODS: Fifteen normal-hearing patients with tinnitus were treated with the neurofeedback protocol. The Tinnitus Handicap Inventory and Visual Analogue Scales were administered before and after treatment and at 1, 3 and 6 months post-treatment. RESULTS: After therapy, all questionnaires scores were significant improved, and the improvements persisted throughout the followup period. Moreover, an increasing trend in the tau/delta ratio was observed; specifically, the trend was more stable respect of the pre-recording measure. However, only in some subjects may the signal alone be enough to develop the correct behaviors. CONCLUSION: Further studies are necessary to characterize the tinnitus subjects who recovered from and adapted to this psychophysical condition and, therefore, responded to neurofeedback therapy.

Assessment of dysphonia due to benign vocal fold lesions by acoustic and aerodynamic indices: a multivariate analysis.

The goal was to identify acoustic and aerodynamic indices that allow the discrimination of a benign organic dysphonic voice from a normal voice. Fifty-three patients affected by dysphonia caused by vocal folds benign lesions, and a control group were subjected to maximum phonation time (MPT) measurements, GRB perceptual evaluations and acoustic/aerodynamic tests. All analyzed variables except the airflow variation coefficient were significantly different between the two groups. The unique significant factors in the discrimination between healthy and dysphonic subjects were the aerodynamic indices of MPT and Glottal efficiency index, and the acoustic index Shimmer. These results show that a combination of three parameters can discriminate a voice deviance and highlight the importance of a multidimensional assessment for objective voice evaluation.

Tinnitus patients lost to follow-up.

Tinnitus patients without hearing loss or hyperacusis often start tinnitus retraining therapy but do not return to the tinnitus clinic for follow-up visits. The aim of this study was to evaluate how these 'missing patients' feel and whether they still use their sound generators after they discontinue retraining therapy. We interviewed 269 tinnitus patients by phone who never returned to the clinic after receiving initial counseling and a generator for sound enrichment. Twenty-six percent did not have tinnitus anymore, 30.5% still used the sound generator to treat their tinnitus, and 43.5% did not use their sound generator but still suffered from tinnitus. This study suggests that therapists need to contact missing patients periodically to follow their improvement, encourage them, and decide on new therapeutic approaches as necessary.