Sexuality Assessment of the Brazilian Population: An Integrative Review of the Available Instruments.

This paper provides an integrative review of psychometric instruments targeting sexual function and clinical measures of sexuality available to the Brazilian population. Our aim was to summarize the existing measures, indicating current development needs related to the quality of psychometric evidence, research design and untapped theoretical ground that could be relevant for clinical practice and research in sexuality. Electronic databases were searched. Additional records were found through a manual search. The general search terms and operators were (scale OR inventory OR questionnaire) AND (validation) AND (sexual beliefs OR sexuality OR sexual behavior OR sexual function OR sexual satisfaction) AND (Brazil or Brazilian). The results indicate a total of 18 developed or transculturally adapted and/or validated scales and questionnaires available in Brazilian Portuguese, covering sexual dysfunctions and clinical measures. Despite development, adaptation and validation efforts, there is a critical need for better psychometric and sampling strategies as well as norms for the clinical interpretation of test results. Ecological validity is also a challenge. At present, sexual assessments in Brazil offer some useful information, but reaching the applied clinical field remains a challenge.Supplemental data for this article is available online at https://doi.org/10.1080/0092623X.2022.2035869 .

The effects of dehydroepiandrosterone on sexual function: a systematic review.

OBJECTIVE: Faced with the growing interest about the action of dehydroepiandrosterone (DHEA) and its benefits, as well as the negative impacts that sexual dysfunctions have on people's quality of life, this systematic review was undertaken with the objective of evaluating the effect of DHEA use on aspects of sexual function. METHOD: An electronic search was conducted in the databases of PubMed, ISI Web of Science and Virtual Health Library (VHL) combining the terms 'DHEA treatment' and 'DHEA use' with terms such as 'sexual dysfunction', 'sexual frequency' and 'libido'. No limits on time and language were imposed. Clinical studies were considered eligible where individuals for any reason made use of DHEA and if they had any aspect of sexual function assessed. Preclinical studies and systematic reviews were considered ineligible. RESULTS: The search identified 183 references and 38 were considered eligible. DHEA improved aspects such as sexual interest, lubrication, pain, arousal, orgasm and sexual frequency. Its effect was better in populations with sexual dysfunction, especially in perimenopausal and postmenopausal women. CONCLUSION: Considering the studies currently published, DHEA is effective in improving several aspects of sexual function, but this effect did not reach all the populations studied.

Erythrocyte phosphoglucomutase activity of bipolar I patients currently using lithium or carbamazepine.

Lithium has been used for the last five decades to treat bipolar disorder, but the molecular basis of its therapeutic effect is unknown. Phosphoglucomutase is a key enzyme in the metabolism of glycogen. In yeast, rabbit and human HEK293 cells, it is inhibited by lithium in the therapeutic concentration range. We measured the phosphoglucomutase activity in erythrocytes and the inhibitor constant for lithium in a population of healthy subjects and compared them to those of bipolar patients treated with lithium or carbamazepine. The specific activity of phosphoglucomutase measured in vitro in erythrocytes from control subjects presented a normal distribution, with the difference between the lowest and the highest activity being approximately 2-fold (0.53-1.10 nmol mg Hb-1 min-1). Comparison of phosphoglucomutase activity in untreated bipolar patients and control subjects showed no significant difference, whereas comparison between bipolar patients treated with carbamazepine or lithium revealed significantly lower mean values in patients treated with carbamazepine (747.3 +/- 27.6 vs 879.5 +/- 35.9 pmol mg Hb-1 min-1, respectively). When we studied the concentration of lithium needed to inhibit phosphoglucomutase activity by 50%, a bimodal distribution among the population tested was obtained. The concentration of LiCl needed to inhibit phosphoglucomutase activity by 50% was 0.35 to 1.8 mM in one group of subjects and in the other it was 3 to 4 mM. These results suggest that phosphoglucomutase activity may be significant in patients with bipolar disorder treated with lithium and carbamazepine.

Dysfunction in the coagulation system and schizophrenia.

Although different hypotheses have been formulated to explain schizophrenia pathogenesis, the links between them are weak. The observation that five psychotic patients on chronic warfarin therapy for deep-vein thrombosis showed long-term remission of psychotic symptoms made us suspect that abnormalities in the coagulation pathway, specifically low tissue plasminogen activator (tPA) activity, could be one of the missing links. Our hypothesis is supported by a high prevalence of conditions affecting tPA activity in drug-naive schizophrenia, such as antiphospholipid antibodies, elevated cytokine levels, hyperinsulinemia and hyperhomocysteinemia. We recently screened a group of schizophrenia patients and controls for conditions affecting tPA activity. Free-protein S deficiency was highly prevalent among patients, but not found in controls. Free-protein S and functional protein C are natural anticoagulants that form complexes that inhibit tPA inhibitors. All participants had normal protein C levels, suggesting that protein S could have a role in schizophrenia, independent of protein C. Chronic patients and those studied during acute episodes had between three and six conditions affecting tPA and/or protein S activity, while patients in remission had up to two, which led us to postulate that multiple conditions affecting tPA and/or protein S activity could contribute to the full expression of schizophrenia phenotype. This paper describes the physiological roles of tPA and protein S, reviewing how their activity influences pathogenesis and comorbidity of schizophrenia. Next, it analyzes how activity of tPA and protein S is influenced by biochemical abnormalities found in schizophrenia. Last, it suggests future directions for research, such as studies on animal models and on therapeutic approaches for schizophrenia aiming at increasing tPA and protein S activity.

Sexual dysfunction in arterial hypertension women: The role of depression and anxiety.

INTRODUCTION: Although high blood pressure is known to be associated with sexual dysfunction, this phenomenon has been little studied in females and has received little intervention in clinical practice. OBJECTIVE: To identify the presence of sexual dysfunction, considering the different possible domains and to evaluate its relationship with the presence of symptoms of anxiety and depression in women with arterial hypertension. METHODOLOGY: One hundred fifty seven women (from 56.4 years) with a diagnosis of arterial hypertension were evaluated with media through the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: High rates of sexual dysfunction were detected in the women evaluated, and this dysfunction was in all domains as follows: desire (68.2%), excitement (68.2%), lubrication (41.1%), orgasm (55.4%), satisfaction (66.42%) and pain (56.1%). Elevated rates of symptoms of anxiety (43.3%) and depression (26.8%) were also found in our sample. Nevertheless, in the present study, such symptoms showed no relationship with sexual dysfunction levels for any of the domains assessed. CONCLUSION: Hypertensive patients exhibit an elevated presence of sexual dysfunction, as well as anxious and depressive symptoms. Although the literature on female sexuality indicates influences of these symptoms on sexual functions, this study did not identify such a relationship in the studied population. Sexuality is an important element in patient quality of life, and a broad understanding of female sexual function is fundamental for good follow-up in these patients.

Moclobemide, imipramine, and placebo in the treatment of major depression (DSM III).

Seventy five patients, diagnosed according to the Structured Clinical Interview for DMS III ("unipolar", Major depression, single or recurrent, with or without melancholia) were treated, in a double-blind fashion, with either moclobemide, imipramine or placebo, during six weeks. The three treatment groups were homogeneous as far as demographic and clinical characteristics were concerned. Patients were in their forties, predominantly females and with long lasting (more than six months) episodes of moderate or severe depressions. From day seven onwards most patients took moclobemide 600 mg/d, imipramine 200 mg/d or 6 caps/d of placebo; only two cases took lower dosages due to intolerance. There were eleven drop-outs, evenly scattered among the three groups. Outcome assessed by means of the Hamilton Scale for Depression and Global Efficacy Evaluations showed a very significant superiority of the two active drugs over placebo. The efficacy of the two drugs was comparable. Side effects were significantly more frequent and more severe in the imipramine group. The tolerability of moclobemide was similar to placebo. These findings are discussed in relation to methodological issues. They point to the conclusion, that moclobemide may be the true "second generation antidepressant", comparably efficacious to the traditional compounds, producing far less side-effects, and because it is reversible, not requiring dietary or drug restrictions in clinical practice.

The long-term treatment of social phobia with moclobemide.

Patients meeting the social phobia criteria of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) on the DSM-III-R Structured Clinical Interview (n = 101) entered a long-term moclobemide treatment study. These patients were treated for 2 years with moclobemide (phase I) followed by drug withdrawal, in most cases abruptly (phase II). Those who relapsed entered phase III for a further period of 2 years of treatment. During phase I 40 patients (39.6%) withdrew due to inefficacy or relapse. Two patients were removed from the study because of other diagnoses (borderline or schizophreniform). At the end of phase I the remaining patients (58.4%) were rated as not ill (45.5%) or minimally ill (11.9%). Effort was taken to achieve the maximum dose of moclobemide (750 mg/day) and the mean (+/-SD) dose was 723.3 +/- 67.7 mg/day (month 21). A marked decrease in symptoms in the patients who responded was recorded on the Liebowitz Scale for Social Phobia, Clinical Global Impressions. Hamilton Anxiety Scale and Hamilton Depression Scale. Non-response was mainly associated with co-morbidity, especially alcohol abuse, axis II disorders, and a history of major depression or secondary dysthymia. The drug was well tolerated; the more frequent side effects were mild and occurred mainly in the first 2 months of phase I, including nausea, headaches or insomnia. In phase II there was a relapse rate of 88% and 51 patients entered phase III; these patients are still being treated.

Hyperventilation challenge test in panic disorder and depression with panic attacks.

Our aim was to determine whether panic disorder (PD) patients, major depressive patients without panic attacks (MD) and major depressive patients with panic attacks (MDP) respond similarly to hyperventilation challenge tests. We randomly selected 35 PD patients, 33 MDP patients, 27 MD patients and 30 normal volunteers with no family history of anxiety or mood disorder. The patients had not been treated with psychotropic drugs for at least 1 week. They were induced to hyperventilate (30 breaths/min) for 4 min, and anxiety was assessed before and after the test. A total of 16 (45.7%) PD patients, 12 (36.4%) MDP patients, four (11.1%) MD patients, and two (6.7%) normal volunteers had a panic attack after hyperventilating. The PD and MDP patients were significantly more responsive to hyperventilation than the MD patients and the normal volunteers. The MD patients had a significantly lower heart-rate response to the test than all the other groups. There is growing evidence that PD patients are more sensitive to the vasoconstrictive effects on basilar arterial blood flow caused by hyperventilation-induced hypocapnia than are comparison subjects. Our data suggest that there is an association between panic attacks and hyperreactivity to an acute hyperventilation challenge test.

Double-blind acute clonazepam vs. placebo in carbon dioxide-induced panic attacks.

The inhalation of 35% carbon dioxide has consistently been shown to provoke panic attacks in panic disorder patients. We aim to determine if an acute dose of clonazepam (2 mg) attenuates the panic attacks induced by an inhalation of 35% carbon dioxide in panic disorder. Twenty-two panic disorder patients who had been drug-free for 1 week participated in a carbon dioxide challenge test 1 h after a dose of either 2 mg of clonazepam or placebo with a randomized double-blind method. Also in a double-blind design during the tests the patients inhaled either atmospheric compressed air ('placebo control') or the carbon dioxide mixture. All patients participated in both tests which were done with a 20-min interval. Immediately before and after the inhalation, the anxiety levels and the symptoms of panic were always assessed. In the clonazepam group (n=11) two patients (18.2%) had a mild panic attack and in the placebo group (n=11) nine patients (81.8%) had a moderate to severe panic attack in the CO(2) challenge test. No patient had panic attacks during inhalation of atmospheric compressed air although anticipatory anxiety levels tended to be higher than in the CO(2) tests. After the CO(2) test anxiety levels were significantly greater in the CO(2) group (three-way ANOVA with Geisser-Greenhouse adjustments, F(31.92,1.86)=17.15, d.f.=7, P=0.013). Although a small sample was studied, the findings suggest the efficacy of an acute dose of clonazepam in attenuating panic attacks induced by carbon dioxide inhalation.

Relationship between mouth and esophageal pressures in different body postures.

Static voluntary efforts, both inspiratory and expiratory (executed with the glottis open against a closed airway) are commonly utilized for the evaluation of correct esophageal balloon positioning for indirect pleural pressure measurement. Agreement between delta Pm (change in mouth pressure) and delta Pes (change in esophageal pressure) indicates the valid indirect determination of pleural pressure. Measurements of delta Pes are more commonly made with the thorax in the upright position, and some investigators have reservations about determinations carried out in the supine position. In the present investigation, the airway shutter occlusion test as well as Müller's maneuver were applied to patients sitting in a plethysmographic box to determine the validity of delta Pes in several body positions. Measurements were made on 8 patients sitting with the thorax in the vertical (90 degrees) position and at angles of 45 degrees, 0 degree and -10 degrees. Thoracic gas volume was also determined at each angle studied. The esophageal balloon was shown to need frequent repositioning when body position was changed. With proper care, valid delta Pes measurements could be made in all positions studied. A plot of the delta Pes/delta POm ratio showed values closer to one for the "occlusion test" than for Müller's maneuver. Phase differences between delta Pes and delta Pm were very small in different body positions. Cardiac artifacts in esophageal measurements were more pronounced in the horizontal and -10 degrees positions. The "occlusion test" is particularly useful for clinical application because it does not require patient cooperation and is a very simple technique for evaluating correct esophageal catheter placement.

Respiratory panic disorder subtype and sensitivity to the carbon dioxide challenge test.

The aim of the present study was to verify the sensitivity to the carbon dioxide (CO2) challenge test of panic disorder (PD) patients with respiratory and nonrespiratory subtypes of the disorder. Our hypothesis is that the respiratory subtype is more sensitive to 35% CO2. Twenty-seven PD subjects with or without agoraphobia were classified into respiratory and nonrespiratory subtypes on the basis of the presence of respiratory symptoms during their panic attacks. The tests were carried out in a double-blind manner using two mixtures: 1) 35% CO2 and 65% O2, and 2) 100% atmospheric compressed air, 20 min apart. The tests were repeated after 2 weeks during which the participants in the study did not receive any psychotropic drugs. At least 15 of 16 (93.7%) respiratory PD subtype patients and 5 of 11 (43.4%) nonrespiratory PD patients had a panic attack during one of two CO2 challenges (P = 0.009, Fisher exact test). Respiratory PD subtype patients were more sensitive to the CO2 challenge test. There was agreement between the severity of PD measured by the Clinical Global Impression (CGI) Scale and the subtype of PD. Higher CGI scores in the respiratory PD subtype could reflect a greater sensitivity to the CO2 challenge due to a greater severity of PD. Carbon dioxide challenges in PD may define PD subtypes and their underlying mechanisms.

Clinical features of panic patients sensitive to hyperventilation or breath-holding methods for inducing panic attacks.

Our aim was to compare the clinical features of panic disorder (PD) patients sensitive to hyperventilation or breath-holding methods of inducing panic attacks. Eighty-five PD patients were submitted to both a hyperventilation challenge test and a breath-holding test. They were asked to hyperventilate (30 breaths/min) for 4 min and a week later to hold their breath for as long as possible, four times with a 2-min interval. Anxiety scales were applied before and after the tests. We selected the patients who responded with a panic attack to just one of the tests, i.e., those who had a panic attack after hyperventilating (HPA, N = 24, 16 females, 8 males, mean age +/- SD = 38.5 +/- 12.7 years) and those who had a panic attack after breath holding (BHPA, N = 20, 11 females, 9 males, mean age +/- SD = 42.1 +/- 10.6 years). Both groups had similar (chi(2) = 1.28, d.f. = 1, P = 0.672) respiratory symptoms (fear of dying, chest/pain discomfort, shortness of breath, paresthesias, and feelings of choking) during a panic attack. The criteria of Briggs et al. [British Journal of Psychiatry, 1993; 163: 201-209] for respiratory PD subtype were fulfilled by 18 (75.0%) HPA patients and by 14 (70.0%) BHPA patients. The HPA group had a later onset of the disease compared to BHPA patients (37.9 +/- 11.0 vs 21.3 +/- 12.9 years old, Mann-Whitney, P < 0.001), and had a higher family prevalence of PD (70.8 vs 25.0%, chi(2) = 19.65, d.f. = 1, P = 0.041). Our data suggest that these two groups--HPA and BHPA patients--may be specific subtypes of PD.

Smoking and psychiatric disorders: a comorbidity survey.

Epidemiological and clinical studies have shown a positive correlation between smoking and psychiatric disorders. To investigate the prevalence of cigarette smoking, 277 psychiatric outpatients with anxiety or depressive disorders (DSM-IV) answered a self-evaluation questionnaire about smoking behavior and were compared with a group of 68 control subjects. The diagnoses (N = 262) were: 30.2% (N = 79) major depressive disorder, 23.3% (N = 61) panic disorder, 15.6% (N = 41) social anxiety disorder, 7.3% (N = 19) other anxiety disorders, and 23.7% (N = 62) comorbidity disorders. Among them, 26.3% (N = 69) were smokers, 23.7% (N = 62) were former smokers and 50.0% (N = 131) were nonsmokers. The prevalence of nicotine dependence among the smokers was 59.0% (DSM-IV). The frequency of cigarette smoking did not show any significant difference among the five classes of diagnosis. The social anxiety disorder patients were the heaviest smokers (75.0%), with more unsuccessful attempts to stop smoking (89.0%). The frequency of former smokers was significantly higher among older subjects and nonsmokers were significantly younger (chi2 = 9.13, d.f. = 2, P = 0.01). Our data present some clinical implications suggesting that in our psychiatric outpatient sample with anxiety disorder, major depression and comorbidity (anxiety disorder and major depression), the frequency of cigarette smoking did not differ from the frequency found in the control group or in general population studies. Some specific features of our population (outpatients, anxiety and depressive disorders) might be responsible for these results.

Hyperventilation in panic disorder patients and healthy first-degree relatives.

Our aim was to observe the induction of panic attacks by a hyperventilation challenge test in panic disorder patients (DSM-IV) and their healthy first-degree relatives. We randomly selected 25 panic disorder patients, 31 healthy first-degree relatives of probands with panic disorder and 26 normal volunteers with no family history of panic disorder. All patients had no psychotropic drugs for at least one week. They were induced to hyperventilate (30 breaths/min) for 4 min and anxiety scales were applied before and after the test. A total of 44.0% (N = 11) panic disorder patients, 16.1% (N = 5) of first-degree relatives and 11.5% (N = 3) of control subjects had a panic attack after hyperventilating (chi(2) = 8.93, d.f. = 2, P = 0.011). In this challenge test the panic disorder patients were more sensitive to hyperventilation than first-degree relatives and normal volunteers. Although the hyperventilation test has a low sensitivity, our data suggest that there is no association between a family history of panic disorder and hyperreactivity to an acute hyperventilation challenge test. Perhaps cognitive variables should be considered to play a specific role in this association since symptoms of a panic attack and acute hyperventilation overlap.

Pharmacotherapy of dysthymia: review and new findings.

Open trials with tricyclics, classical monoamine oxidase inhibitors (MAOIs) or lithium in dysthymia yielded a response rate in 45% of subjects. A long-term treatment of dysthymia with 276 patients treated during 4 years with either moclobemide, tranylcypromine or a combination of amitryptiline plus chlordiazepoxide is described. After discontinuation there was a relapse rate of 89.1%. The controlled studies with tricyclics, MAOIs, reversible inhibitors of monoamine oxidase (RIMAs), specific serotonin reuptake inhibitor (SSRIs) or benzamides showed that drugs well-tolerated work better in dysthymia, due to the fact that the treatment must be long-term. Sertraline was studied vs placebo or imipramine in primary dysthymia. Moclobemide, imipramine and placebo were also studied in 315 patients. Mean doses were 650 mg/d of moclobemide and 203.2 mg/d of imipramine. Moclobemide and sertraline were both efficacious and well tolerated. In a long term treatment the clinician should assess the risk-benefit ratio. Dysthymic patients are very sensitive to unwanted effects and compliance is a serious issue.

Antidepressants in social anxiety disorder.

Social anxiety disorder (SAD) is a marked and persistent fear of doing almost everything in front of people due to concerns about being judge by others. An up-to-date review is needed in order to reach a practical judgement of all psychopharmacological data. Case reports, open and double-blind trials with SAD were described and commented upon from a clinical point of view. The MEDLINE system was searched from 1975 to 2001. The references from the selected papers were also used as a source. MAOIs (fenelzine, tranylcypromine), reversible monoamino oxidase-A inhibitors (moclobemide, brofaromine), SSRIs (paroxetine, sertraline, fluoxetine, fluvoxamine) and some other antidepressants (venlafaxine, nefazodone) have proven effective in several studies with various methodologies. The MAOIs have more serious adverse effects and the SSRIs have the best tolerance. SSRIs are efficacious and the first choice of treatment.

Carbon dioxide induced panic attacks and short term clonazepam treatment. Preliminary study.

AIMS: 1. To verify the sensibility of panic patients to a mixture of 35% CO2 and 65% O2. 2. To determine if a ten days treatment with clonazepam attenuates the panic attacks induced by the inhalation of 35% carbon dioxide in panic disorder. METHOD: We randomly selected six panic disorder subjects, using the Structured Clinical Interview for DSM-IV. All subjects went double-blindly through an inhalation of 35% CO2 and compressed gas (atmospheric air) on two occasions. First, at baseline, when they were drug free. Second, after a 10 days clonazepam treatment. RESULTS: Neither at baseline nor after treatment any patient had a panic attack during compressed gas inhalation. At the first test five patients (83.3%) had a severe panic attack with high levels of subjective anxiety during carbon dioxide inhalation. After 9.6 (+/- 3.4) days of clonazepam treatment, only two (33.3%) patients experienced a mild panic attack. CONCLUSION: This pilot study suggests the efficacy of the short term clonazepam therapy in attenuating panic attacks and supports the usefulness of the 35% carbon dioxide challenge test as an analogue method for study the efficacy of anti-panic drugs. Further placebo-controlled studies to pharmacological treatment are warranted.

Double-blind clonazepam vs placebo in panic disorder treatment.

OBJECTIVE: To assess the effectiveness of clonazepam, in a fixed dose (2 mg/day), compared with placebo in the treatment of panic disorder patients. METHOD: 24 panic disorder patients with agoraphobia were randomly selected. The diagnosis was obtained using the structured clinical interview for DSM-IV. All twenty-four subjects were randomly assigned to either treatment with clonazepam (2 mg/day) or placebo, during 6 weeks. Efficacy assessments included: change from baseline in the number of panic attacks; CGI scores for panic disorder; Hamilton rating scale for anxiety; and panic associated symptoms scale. RESULTS: At the therapeutic endpoint, only one of 9 placebo patients (11.1%) were free of panic attacks, compared with 8 of 13 (61.5%) clonazepam patients (Fisher exact test; p=0,031). CONCLUSION: the results provide evidence for the efficacy of clonazepam in panic disorder patients.

Panic disorder and hyperventilation.

UNLABELLED: Respiratory abnormalities are associated with anxiety, particularly with panic attacks. Symptoms such as shortness of breath, "empty-head" feeling, dizziness, paresthesias and tachypnea have been described in the psychiatric and respiratory physiology related to panic disorder. Panic disorder patients exhibit both behaviorally and physiologically abnormal responses to respiratory challenges tests. OBJECTIVE: We aim to observe the induction of panic attacks by hyperventilation in a group of panic disorder patients (DSM-IV). METHOD: 13 panic disorder patients and 11 normal volunteers were randomly selected. They were drug free for a week. They were induced to hyperventilate (30 breaths/min) for 3 minutes. Anxiety scales were taken before and after the test. RESULTS: 9 (69.2%) panic disorder patients and one (9.1%) of control subjects had a panic attack after hyperventilating (p < 0.05). CONCLUSION: The panic disorder group was more sensitive to hyperventilation than normal volunteers. The induction of panic attacks by voluntary hyperventilation may be a useful and simple test for validating the diagnosis in some specific panic disorder patients.

Tinnitus and its association with psychiatric disorders: systematic review.

OBJECTIVES: To systematically review the literature on the occurrence of psychiatric diagnoses in a tinnitus-affected population, and correlate the presence of psychiatric disorders with tinnitus-related annoyance and severity. METHOD: A systematic review of the literature published between January 2000 and December 2012 was performed using PubMed, ISI Web of Science and SciELO databases. Original articles in English and Portuguese that focused on the diagnosis of mental disorders associated with tinnitus, especially anxiety and depression, were identified. RESULTS: A total of 153 articles were found and 16 were selected. Fifteen articles showed a high prevalence of psychiatric disorders in tinnitus-affected patients, and nine showed a high correlation between the presence of a psychiatric disorder and tinnitus-related annoyance and severity. CONCLUSION: The prevalence of psychiatric disorders, especially anxiety and depression, is high in tinnitus patients, and the presence of these disorders correlates with tinnitus-related annoyance and severity.