Association Of Tinnitus Research Articles

Evaluation of Gene Variants in TGFB1, SERPINF1 and MEPE in a Spanish Family Affected by Otosclerosis and Tinnitus

Otosclerosis (OTSC) is a common type of deafness affecting up to 0.4 % of Caucasians. Its familial form is inherited in an autosomal dominant fashion, although to this date, no definitive cause for OTSC has been found. In the development of OTSC, three recent genetic association studies have suggested the participation of particular point mutations and small indels in the TGFB1, SERPINF1, and MEPE genes. Consequently, replicative studies are needed to confirm the role of the proposed mutations in OTSC patients. The goal of this study was to test the presence of the candidate variants described in the genes TGFB1, SERPINF1, and MEPE in a new case of familial OTSC with seven affected individuals. DNA was extracted from saliva samples of a Spanish family with several members affected by OTSC. PCR amplified target regions of some candidate genes, and the products were purified, Sanger-sequenced, and analyzed in silico. The family subject of the study did not carry the candidate variants for OTSC described in the genes TGFB1, SERPINF1, and MEPE, although it cannot be ruled out the involvement of other mutations in genes related to their same signaling pathways. This result highlights the importance of performing replicative studies for complex diseases, such as OTCS, in families of diverse origins. Additionally, a significant association of subjective tinnitus with OTSC has been found in this family, although the link between the two pathologies should be studied further.

Risks of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache.

Tinnitus and hearing impairment are prevalent among headache patients. This study aims to investigate the risk of tinnitus, sensorineural hearing impairment, and sudden deafness in patients with non-migraine headache. Participants included 43 294 patients with non-migraine headache (non-migraine headache cohort) and 173 176 patients with no headache of any type (control cohort) frequency-matched with respect to 10-year age interval and sex from the Longitudinal Health Insurance Database 2005 of the Taiwan National Health Insurance Research Database. The mean age of the non-migraine headache cohort was 28.4 ± 14.9 years, and 58.5% of this cohort was male. The incidence rates of tinnitus, sensorineural hearing impairment, and sudden deafness were compared between cohorts using the Kaplan–Meier method with the log-rank test. A Cox proportional hazard model was used to examine the association of tinnitus, sensorineural hearing impairment, and sudden deafness with non-migraine headache, with adjustment for all covariates. The combined risk of either tinnitus, sensorineural hearing impairment, or sudden deafness was higher in the non-migraine headache cohort than in the control cohort (adjusted odds ratio [aHR], 2.73; 95% confidence interval [95% CI], 2.62–2.84; p < 0.0001). Subgroup analysis showed that patients in the non-migraine headache cohort were at significantly higher risk of developing tinnitus (aHR, 3.05; 95% CI, 2.91–3.19; p < 0.0001), sensorineural hearing impairment (aHR, 1.89; 95% CI, 1.74–2.05; p < 0.0001), and sudden deafness (aHR, 2.14; 95% CI, 1.77–2.59; p < 0.0001) than were controls. In this population-based study, the risks of tinnitus, sensorineural hearing impairment, and sudden deafness were found to be significantly higher in patients with non-migraine headache than in those without headache.

Sex-Specific Association of Tinnitus With Suicide Attempts

Sex-Specific Association of Tinnitus With Suicide Attempts

Tinnitus and its relationship with anxiety and depression in the elderly: a systematic review

ABSTRACT Objective: to verify, in the literature, a probable association of tinnitus with anxiety and depression in the elderly. Methods: a systematic review (through a search in the indexed databases - Lilacs, Scielo, Pubmed, Science Direct, The Cochrane Library) of studies published between 2013 and 2018, in Portuguese and in English, involving adults and/or elderly (18 years and older). The descriptors used were: “tinnitus", "depression", "anxiety", "adult", "elderly", interspersed by the Boolean operator AND. Results: 11 studies were selected, from which, 5 compared adults to elderly and only 2 evaluated such relationship in the elderly alone. Studies suggest that, as age increases, tinnitus severity and psychological symptoms also increase, affecting both men and women. Conclusion: few studies compared the relationship between the variables among the elderly. A probable association between the variables for both genders has been found, suggesting that the advancing age contributes to the increase of tinnitus severity and its psychological symptoms, affecting the quality of life of these individuals. Further studies are suggested to confirm the association between tinnitus, anxiety and depression in the elderly. Multi-professional work is important for the evaluation and treatment of these people.

Association of Tinnitus and Other Cochlear Disorders With a History of Migraines

ImportanceA headache is a symptom of a migraine, but not all patients with migraine have headaches. It is still unclear whether a migraine might increase the risk of cochlear disorders, even though a migraine does not occur concurrently with cochlear disorders.ObjectiveTo investigate the risk of cochlear disorders for patients with a history of migraines.Design, Setting, and ParticipantsThis study used claims data from the Taiwan Longitudinal Health Insurance Database 2005 to identify 1056 patients with migraines diagnosed between January 1, 1996, and December 31, 2012. A total of 4224 controls were also identified from the same database based on propensity score matching. Statistical analysis was performed from January 23, 1996, to December 28, 2012.Main Outcomes and MeasuresThe incidence rate of cochlear disorders (tinnitus, sensorineural hearing impairment, and/or sudden deafness) was compared between the cohorts by use of the Kaplan-Meier method. The Cox proportional hazards regression model was also used to examine the association of cochlear disorders with migraines.ResultsOf the 1056 patients with migraines, 672 were women and 384 were men, and the mean (SD) age was 36.7 (15.3) years. Compared with the nonmigraine cohort, the crude hazard ratio for cochlear disorders in the migraine cohort was 2.83 (95% CI, 2.01-3.99), and the adjusted hazard ratio was 2.71 (95% CI, 1.86-3.93). The incidence rates of cochlear disorders were 81.4 (95% CI, 81.1-81.8) per 1 million person-years for the migraine cohort and 29.4 (95% CI, 29.2-29.7) per 1 million person-years for the nonmigraine cohort. The cumulative incidence of cochlear disorders in the migraine cohort (12.2%) was significantly higher than that in the matched nonmigraine cohort (5.5%). Subgroup analysis showed that, compared with the nonmigraine cohort, the adjusted hazard ratios in the migraine cohort were 3.30 (95% CI, 2.17-5.00) for tinnitus, 1.03 (95% CI, 0.17-6.41) for sensorineural hearing impairment, and 1.22 (95% CI, 0.53-2.83) for sudden deafness.Conclusions and RelevanceIn this population-based study, the risk of cochlear disorders, especially for tinnitus, was found to be significantly higher among patients with a history of migraines. This finding may support the presence and/or concept of “cochlear migraine.”

Epidemiology of Clinically Significant Tinnitus: A 10-Year Trend From Nationwide Health Claims Data in South Korea.

Prevalence of tinnitus has been reported to vary according to the target population and definition of tinnitus. To improve the understanding of tinnitus, authors used the nation-wide health claim data to study the tinnitus in the entire population of South Korea. Retrospective big data review. Analysis of big data from the National Health Information Database. Patients diagnosed with tinnitus according to International Classification of Diseases code 10th edition (ICD-10) and requested to receive National Health Insurance claim at least once from January 2006 to December 2015. None. Epidemiologic data, association of tinnitus with the otologic and systemic diseases. The number of patients who received medical care because of tinnitus was 1.44% (0.78 million per 51 million) in 2015. There was a higher prevalence of tinnitus in women, and the overall prevalence increased with increasing age of patients and peaked at patients in their 70s (4.43%). The prevalence of tinnitus among patients aged 10 to 30 years, showed a tendency to increase during study period. In the regional analysis, highest prevalence was observed in Gwangju (2.02%). In comparison with the control group, the patients with tinnitus showed a higher frequency in otologic and systemic disease. Especially, noise induced hearing loss (adjusted odds ratio [AOR] = 82.1, 95% confidence interval [95% CI] = 74.8-90.2) and sudden sensorineueal hearing loss (AOR = 49.7, 95% CI = 48.4-51.0) showed high frequency in tinnitus patient group. The prevalence and incidence of tinnitus in this study for entire nation were lower than previously reported studies. These results have limitation because the study only covered patient using the medical service for tinnitus and missed tinnitus sufferers not seeking medical service. However, this study is meaningful in that it was targeting entire nation, reflected the characteristics of clinically significant tinnitus patient enough to visit medical service.

Postoperative Tinnitus After Vestibular Schwannoma Surgery Depends on Preoperative Tinnitus and Both Pre- and Postoperative Hearing Function.

Tinnitus is one of the most common symptoms before and/or after the surgical removal of a vestibular schwannoma (VS) affecting almost half of the patients. Although there is increasing evidence for the association of hearing impairment and VS-associated tinnitus, the effect of hearing deterioration due to surgery and its relation to the postoperative tinnitus (postTN) is poorly investigated. This knowledge, however, might (i) enlighten the pathophysiology of VS-associated tinnitus (i.e., peripheral or central origin) and (ii) improve preoperative patient counseling. The aim of this study was to understand the predisposition factors for a postTN in relation to hearing outcome after surgery. This retrospective study analyzed the presence of tinnitus in 208 patients with unilateral VS before and after surgical removal. A binomial logistic regression was performed to ascertain the effect of pre- and postoperative hearing as well as age, gender, tumor side, and size, and intraoperative cochlear nerve resection (CNR) on the likelihood of postoperative VS-associated tinnitus. Preoperative tinnitus was the strongest predictor of postTN. In addition, deterioration of functional hearing was increasing, while functional deafferentation (i.e., postoperative hearing loss) of non-functional hearing was reducing the risk of postTN. At the same time, patients with no preoperative tinnitus but complete hearing loss had the lowest risk to suffer from postTN. Patient age, gender, tumor side, and size as well as CNR played a subordinate role. While the presence of preoperative tinnitus was the strongest predictor of postTN, there is a distinct relationship between hearing outcome and postTN depending on the preoperative situation. Functional or anatomical deafferentation due to surgical tumor removal does not prevent postTN per se.

Is smoking a risk factor for tinnitus? A systematic review, meta-analysis and estimation of the population attributable risk in Germany

ObjectiveTo assess the epidemiological association of smoking status and tinnitus with a systematic review and meta-analysis and to estimate the population attributable risk in Germany.Data sourcesA systematic literature search in...

Tinnitus, depression, and suicidal ideation in adults: A nationally representative general population sample

Tinnitus is strongly associated with psychiatric symptoms, including depression and suicidality. We aimed to further investigate the association of tinnitus with depressive mood and/or suicidal ideation, and explore the shared risk factors for these within a representative sample of the adult general population. We also investigated potential mediation pathways among tinnitus, suicidal ideation, depression, shared risk factors, and perceived stress levels. We analysed data from 28,930 adults (aged ≥19 years) from the fourth and fifth Korea National Health and Nutrition Examination Surveys (KNHANES) conducted from 2008 to 2012 in South Korea. We investigated the presence and severity of tinnitus, depressive mood, suicidal ideation, perceived usual stress level, and socioeconomic and health-related variables. We conducted logistic regression and mediation analyses. Tinnitus and its severity were significantly associated with depressive mood and suicidal ideation. Tinnitus, depressive mood, and suicidal ideation shared common socioeconomic and health-related risk factors. Tinnitus significantly mediated the association of shared risk factors for depressive mood and suicidal ideation. Perceived usual stress level mediates the association of tinnitus with depressive mood and suicidal ideation. The correlation of perceived usual stress levels with depression and suicidal ideation was also mediated by tinnitus. Our findings implicate that tinnitus may contribute substantially to the development of depressive symptom and suicidal ideation in adults via apparent interactions with shared risk factors and stress levels.

Positive Association between Tinnitus and Arterial Hypertension.

Tinnitus is the perception of noise in the absence of an external source and is considered by most authors as a multifactorial symptom. A systematic review concerning the association of tinnitus and systemic arterial hypertension retrieved suggestions of a positive association, but the articles included failed to perform a detailed analysis on the theme. To analyze the presence of arterial hypertension in tinnitus and non-tinnitus patients, to analyze differences between tinnitus impact and psychoacoustic measurements in hypertensive and normotensive patients, and to evaluate the association between the presence of tinnitus and the diverse antihypertensive drugs employed. This includes cross-sectional transversal study, comparing two groups of subjects (144 in the study group with tinnitus and 140 in the control group without tinnitus). Clinical, demographical, audiometrical, and psychoacoustics characteristics of the subjects were compared. Hypertension prevalence in tinnitus subjects was 44.4% against 31.4% in subjects without tinnitus (p = 0.024). Positive associations with tinnitus were found with hypertension treatment with angiotensin-converting enzyme (ACE) inhibitors (p = 0.006), tiazidic diuretics (p < 0.0001), potassium-sparing diuretics (p = 0.016), and calcium channels blockers (p = 0.004). There is an association between tinnitus and arterial hypertension. This association is particularly strong in older patients. Hypertension treatment with diuretics, ACE inhibitors, and calcium channels blockers were more prevalent in tinnitus patients, suggesting that an eventual ototoxicity of these drugs may be involved in tinnitus pathophysiology, a hypothesis that should be evaluated in further studies.

Prevalence and associated risk factors of otitis media and its subtypes in South Indian population

Background: Otitis media is a common inflammatory disorder caused by the effusion of fluids or pathological changes in the tympanic membrane of middle ear that leads to hearing loss in all age groups which may be either temporary or permanent. Objective: The present study aimed to identify the risk factors responsible for the onset and progression of otitis media and its subtypes as well as its associated co-morbidities in the South Indian population. Subjects and methods: The study constituted 2602 subjects including children and adults affected with OM and the diagnosis was confirmed by ENT specialists using all the required otorhinolaryngological tests. The study was carried out by the institutional ethical clearance. The data were coded and evaluations were performed using the Statistical Package for Social Sciences, PASW STATISTICS 18.0 software (SPSS Inc., Chicago, IL, USA). Results: squamous-chronic suppurative otitis media was highly prevalent (47.3%) followed by mucosal-chronic suppurative otitis media (18.5%), acute suppurative otitis media (17.6%), and otitis media with effusion (16.6%). The multinomial logistic regression analysis showed significant association of tinnitus with squamous-chronic suppurative otitis media; bilaterality, tinnitus and vertigo with mucosal-chronic suppurative otitis media while bilaterality, adenoids, tinnitus and snoring with otitis media with effusion. Significant differences were observed in different forms of hearing loss at higher frequency within the subtypes of otitis media. Conclusions: The study has revealed that otitis media predominantly affects all age groups and has a serious health concern in cases affected with hearing loss and its associated co-morbidities.

Association of tinnitus and hearing loss in otological disorders: a decade-long epidemiological study in a South Indian population

IntroductionTinnitus is a common disorder that occurs frequently across all strata of population and has an important health concern. Tinnitus is often associated with different forms of hearing loss of varying severity. ObjectiveThe present study aimed to identify the association of tinnitus with hearing loss in various otological disorders of a South Indian population. MethodsA total of 3255 subjects referred to the MAA ENT Hospital, Hyderabad, from 2004 to 2014, affected with various otological diseases have been included in the present cross-sectional study. Diagnosis of the diseases was confirmed by an ear, nose, and throat (ENT) specialist using detailed medical and clinical examination. Statistical analysis was performed using the χ2 test and binary logistic regression. ResultsTinnitus was observed in 29.3% (956) of the total study subjects that showed an increased prevalence in greater than 40 years of age. There was a significant increase in risk of tinnitus with middle (OR=1.79, 95% CI=1.02–3.16) and inner (OR=3.00, 95% CI=1.65–5.45) inner ear diseases. It was noted that 96.9% (n=927) of the tinnitus subjects was associated with hearing loss. Otitis media (60.9%), presbycusis (16.6%) and otosclerosis (14.3%) are the very common otological disorders leading to tinnitus. Tinnitus was significantly associated with higher degree of hearing loss in chronic suppurative otitis media (CSOM) subjects. ConclusionThe present study could identify the most prevalent otological risk factors leading to development of tinnitus with hearing loss in a South Indian population.

Association of Hearing Loss and Tinnitus with Health-Related Quality of Life: The Korea National Health and Nutrition Examination Survey.

BackgroundHearing loss and tinnitus are global public health concerns. There have been some studies suggesting a relationship between hearing loss and tinnitus and impaired health-related quality of life (HRQoL), but there have been no large cross-sectional epidemiologic studies of a representative sample of the entire country population investigating this possible association.ObjectiveThe aim of this study was to investigate the relationship between hearing loss and tinnitus and HRQoL in South Korea using data from the Korea National Health and Nutrition Examination Surveys during 2010–2012.MethodsCross-sectional data of 11,266 adults who completed the Korea National Health and Nutrition Examination Surveys were analyzed. Subjects were divided into four groups as follows: normal hearing without tinnitus, normal hearing with tinnitus, hearing loss without tinnitus, and hearing loss with tinnitus.ResultsAmong the population that was ≥19 years of age, the prevalence of unilateral hearing loss was 9.69% and that of tinnitus in the prior 12 months was 32.76%. The hearing loss with tinnitus group had the highest percentage of subjects who responded “some or extreme problems” in all five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of HRQoL. After adjustment for age, gender, body mass index, smoking status, alcohol intake, regular exercise, house income, education level, diabetes, hypertension, and stress level, the HRQoL odds ratios (OR) were 1.47 (95% confidence interval [CI], 1.07–2.02) for mobility, 1.59 (95% CI, 1.07–2.37) for usual activity, and 1.84 (95% CI, 1.25–2.70) for anxiety/depression in the hearing loss with tinnitus group, compared with the normal hearing without tinnitus group. The ORs for the normal hearing with tinnitus group compared with the hearing loss without tinnitus group was increased in all five dimensions of HRQoL after adjustment for confounders.ConclusionHearing loss with tinnitus has a considerable impact on HRQoL in the Korean population. In our study, the hearing loss without tinnitus group showed better a HRQoL than the normal hearing with tinnitus group.

MENIERE’S DISEASE: UPDATE OF ETIOPATHOGENETIC THEORIES AND PROPOSAL OF A POSSIBLE MODEL OF EXPLANATION

Meniere’s Disease (MD) is an affection consisting of an association of sensorineural hearing loss, tinnitus and vertigo initially presenting by crises. A review of the most considered possible causative factors and pathophysiologic interpretations allows us to underline the uncertainties which still exist about the genesis of this illness. We propose a mechanistic model based on the effect of a haemodynamic imbalance leading to transient ischaemia which could have an effect on the pH of the inner ear as well as on the work of the inner ear proton pumps. It is hypothesized that under ischaemic conditions and consequent metabolic acidity a preserved proton pump activity can generate an overload of anions in the endolymphatic partition, which is a closed system, thus resulting in an enhancement of osmolarity and consequently in the formation of a hydrops resulting in the development of fluctuating hearing loss, tinnitus and vertigo which characterize Meniere’s Disease.

Association of Tinnitus and Electromagnetic Hypersensitivity: Hints for a Shared Pathophysiology?

BackgroundTinnitus is a frequent condition with high morbidity and impairment in quality of life. The pathophysiology is still incompletely understood. Electromagnetic fields are discussed to be involved in the multi-factorial pathogenesis of tinnitus, but data proofing this relationship are very limited. Potential health hazards of electromagnetic fields (EMF) have been under discussion for long. Especially, individuals claiming themselves to be electromagnetic hypersensitive suffer from a variety of unspecific symptoms, which they attribute to EMF-exposure. The aim of the study was to elucidate the relationship between EMF-exposure, electromagnetic hypersensitivity and tinnitus using a case-control design.MethodologyTinnitus occurrence and tinnitus severity were assessed by questionnaires in 89 electromagnetic hypersensitive patients and 107 controls matched for age-, gender, living surroundings and workplace. Using a logistic regression approach, potential risk factors for the development of tinnitus were evaluated.FindingsTinnitus was significantly more frequent in the electromagnetic hypersensitive group (50.72% vs. 17.5%) whereas tinnitus duration and severity did not differ between groups. Electromagnetic hypersensitivity and tinnitus were independent risk factors for sleep disturbances. However, measures of individual EMF-exposure like e.g. cell phone use did not show any association with tinnitus.ConclusionsOur data indicate that tinnitus is associated with subjective electromagnetic hypersensitivity. An individual vulnerability probably due to an over activated cortical distress network seems to be responsible for, both, electromagnetic hypersensitivity and tinnitus. Hence, therapeutic efforts should focus on treatment strategies (e.g. cognitive behavioral therapy) aiming at normalizing this dysfunctional distress network.

Tinnitus with or without hearing loss: are its characteristics different?

The present study was carried out in order to analyze the clinical characteristics of tinnitus both in normal hearing subjects and in patients with hearing loss. The study considered 520 consecutive tinnitus sufferers. The following parameters were considered: age, sex, subjective disturbance caused by tinnitus, subjective judgment of tinnitus intensity, tinnitus laterality, tinnitus duration, tinnitus measurements, normal hearing or associated hearing loss. Among the patients considered, 223 have normal hearing while 297 have a hearing deficit. The hearing impairment was found to be in most cases of sensorineural type. The subjective discomfort is higher in presence of hearing loss. Subjects with hearing loss needed significantly higher masking levels. No evident differences in the residual inhibition (RI) result between the two groups were found. The present study confirms that tinnitus is most frequently associated with hearing loss. The characteristics of tinnitus in normal hearing subjects, except for the subjective judgment of tinnitus intensity, the pitch and the RI, are significantly different for those observed in subjects with hearing loss. The association of tinnitus and hearing deficit seems to increase the perceived severity of the symptom.

Otosclerosis and chronic tinnitus.

Chronic subjective tinnitus is a common feature of clinical otosclerosis. Analysis of the records of 1,014 consecutive cases of clinical otosclerosis, all confirmed by stapes surgery in South Australia between 1960 and 1972, gives a preoperative prevalence of this symptom of 65%. The association of tinnitus with various predictors is considered, and a statistical analysis is presented. Tinnitus has an association with gender (p < .0001), mean preoperative bone conduction (BC) level (p = .0012), mean air conduction (AC) level (p = .0192), and mean air-bone gap (p = .0075). The associations between tinnitus and the age of the patient, the duration of deafness, the presence of Schwartze's sign, and the severity of footplate pathological involvement were all nonsignificant. The association of tinnitus with the AC and BC thresholds is unexpectedly paradoxical. An economic predictive model for tinnitus in otosclerosis has been constructed from the 2 strongly significant variables, gender and mean BC hearing level, by logistic regression. In this large series of cases, the log odds in favor of finding tinnitus are about 0.810 for male subjects and 1.394 for female subjects when the BC level is zero. The log odds fall by 0.014 for each decibel of mean BC rise.

Tinnitus, Psychosis, and Suicide-Reply

Frankenburg and Hegarty make a useful point about the potential association of tinnitus and depression with auditory hallucinations. Depression, when severe or combined with another psychiatric disorder such as schizophrenia, may produce hallucinations and delusions. It is important to note, however, that formed auditory hallucinations are extremely rare in patients with tinnitus. We saw no patients with formed hallucinations among the over 150 depressed patients with tinnitus in our three studies. 1-3 Clinically, it is easy to distinguish formless buzzing, hissing, or ringing from intelligible words. Musical hallucinations are associated with otologic, rather than psychiatric, disease. 4 Whether depression produces auditory hallucinations seems to be more related to the severity of the depression, rather than the presence of tinnitus. Tinnitus is almost always associated with a high-frequency sensorineural hearing loss. Once established, tinnitus becomes louder, more intrusive, and more disabling in the presence of depression. The usual mode of interaction

Tinnitus and vertigo in patients with temporomandibular disorder.

The association of tinnitus and vertigo with temporomandibular disorder (TMD) has been debated for many years. The observation that patients with TMD have otologic symptoms is confounded because tinnitus and vertigo are common symptoms in the normal population. The present study was conducted to determine if tinnitus and vertigo are actually more prevalent in patients with TMD than in appropriate age-matched controls. One control group was recruited from patients seeking care for health maintenance and the other from patients seeking routine dental care. We surveyed 1032 patients: 338 had TMD and 694 served as two age-matched control groups. Tinnitus and vertigo symptoms were significantly more prevalent in the TMD group than in either of the control groups. The mechanism of the association of TMD and otologic symptoms is unknown.

Subjective Head Noises (Tinnitus Aurium): Genesis and Differential Diagnostic Significance: A Few Facts and Several Speculations

Tinnitus, vibratory (intrinsic and extrinsic) and nonvibratory (peripheral and central), and some of the diseases and disorders associated with it are discussed; also discussed are the percentages in many types of ear conditions, variations found in deaf-blind, in adults, and in children, etiological factors, the close association of tinnitus with age, and the incidence of sludge. Tinnitus is compared with itching, and its modes of production and the hearing of beats with tonal tinnitus, monaural and binaural, are also discussed. Details of management and treatment and particularly the usefulness of certain anti-sludging and anti-spasmodic medications, and the importance of a careful history are set forth.