Unequal climate impacts on global values of natural capital.

Ecosystems generate a wide range of benefits for humans, including some market goods as well as other benefits that are not directly reflected in market activity1. Climate change will alter the distribution of ecosystems around the world and change the flow of these benefits2,3. However, the specific implications of ecosystem changes for human welfare remain unclear, as they depend on the nature of these changes, the value of the affected benefits and the extent to which communities rely on natural systems for their well-being4. Here we estimate country-level changes in economic production and the value of non-market ecosystem benefits resulting from climate-change-induced shifts in terrestrial vegetation cover, as projected by dynamic global vegetation models (DGVMs) driven by general circulation climate models. Our results show that the annual population-weighted mean global flow of non-market ecosystem benefits valued in the wealth accounts of the World Bank will be reduced by 9.2% in 2100 under the Shared Socioeconomic Pathway SSP2-6.0 with respect to the baseline no climate change scenario and that the global population-weighted average change in gross domestic product (GDP) by 2100 is -1.3% of the baseline GDP. Because lower-income countries are more reliant on natural capital, these GDP effects are regressive. Approximately 90% of these damages are borne by the poorest 50% of countries and regions, whereas the wealthiest 10% experience only 2% of these losses.

Dimethyl fumarate-induced lymphocyte count drop is related to clinical effectiveness in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Dimethyl fumarate (DMF) causes a mean lymphocyte count drop of approximately 30% in relapsing-remitting multiple sclerosis (RRMS) patients. The relationship between this reduction and DMF effectiveness is controversial. The objective was to investigate if the decrease in absolute lymphocyte count (ALC) from baseline during DMF treatment is associated with clinical and magnetic resonance imaging (MRI) disease activity. A secondary aim was to evaluate ALC variations over time in a real-life cohort of DMF-treated patients. METHODS: Demographic, laboratory, clinical and MRI data were collected in this observational multicentre study, conducted on RRMS patients treated with DMF for at least 6 months. Multivariate Cox models were performed to evaluate the impact of 6-month ALC drop on time to no evidence of disease activity (NEDA-3) status loss. NEDA-3 is defined as absence of clinical relapses, MRI disease activity and confirmed disability progression. RESULTS: In all, 476 patients (312 females, age at DMF start 38.4 ± 9.97 years) were analysed up to 5-year follow-up. A greater lymphocyte decrease was associated with a lower risk of NEDA-3 status loss (hazard ratio 0.87, P = 0.01). A worse outcome in patients with lower ALC drop (<11.5%), compared with higher tertiles (11.5%-40.5% and >40.5%), was observed (P = 0.008). The nadir of ALC drop (-33.6%) and 35% of grade III lymphopaenia cases occurred after 12 months of treatment. CONCLUSION: A higher lymphocyte count drop at 6 months is related to better outcomes in DMF-treated patients. A careful ALC monitoring should be pursued up to 24 months of treatment.

Listening to the neurological teams for multiple sclerosis: the SMART project.

OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses' professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it.

Risk of early relapse following the switch from injectables to oral agents for multiple sclerosis.

BACKGROUND AND PURPOSE: Early relapse outcomes in long-term stable patients switching from interferon ß/glatiramer acetate (IFNß/GA) to oral therapy are unknown. OBJECTIVE: The objective of this study was to compare early relapse and progression in multiple sclerosis (MS) patients switching to oral therapy following a period of stable disease on IFNß/GA, relative to a propensity-matched comparator of patients remaining on IFNß/GA. METHODS: The MSBase cohort study is a global, longitudinal registry for MS. Time to first 6-month relapse in previously stable MS patients switching from platform injectables ('switchers') to oral agents were compared with propensity-matched patients remaining on IFNß/GA ('stayers') using a Cox marginal model. RESULTS: Three-hundred and ninety-six switchers were successfully matched to 396 stayers on a 1:1 basis. There was no difference in the proportion of patients recording at least one relapse in the first 1-6 months by treatment arm (7.3% switchers, 6.6% stayers; P = 0.675). The mean annualized relapse rate (P = 0.493) and the rate of first 6-month relapse by treatment arm (hazard ratio 1.22, 95% confidence interval 0.70, 2.11) were also comparable. There was no difference in the rate of disability progression by treatment arm (hazard ratio 1.43, 95% confidence interval 0.63, 3.26). CONCLUSION: This is the first study to compare early relapse switch probability in the period immediately following switch to oral treatment in a population previously stable on injectable therapy. There was no evidence of disease reactivation within the first 6 months of switching to oral therapy.

Implementation of the 'Sapere Migliora' information aid for newly diagnosed people with multiple sclerosis in routine clinical practice: a late-phase controlled trial.

BACKGROUND: The SIMS-Trial showed that the 'Sapere Migliora' information aid (IA) for newly diagnosed people with multiple sclerosis (PwMS) effectively improved patient knowledge and satisfaction with care. OBJECTIVES: The objectives of this paper are to assess the effectiveness of the IA in clinical practice and to compare the whole IA with the take-home booklet/website component alone. METHODS: After updating the IA and replacing the CD with a website, a prospective, open-label non-randomised controlled trial compared the whole IA (group A, five SIMS-Trial centres) to take-home (group B, 16 centres). One month after the intervention, participants completed the MS Knowledge Questionnaire (MSKQ), care satisfaction questionnaire (COSM-R) (primary study outcomes), Hospital and Anxiety Depression Scale, and ad hoc questionnaire appraising the IA. RESULTS: We enrolled 159 newly diagnosed PwMS (May 2012-March 2013). Drop-outs were four of 77 (5%, group A) and 11/82 (13%, group B). Primary endpoint (highest tertile both for MSKQ and COSM-R section 2 scores) was achieved by 38/77 (49%) group A and 33/82 (40%) group B (p = 0.25). Attainment of secondary outcomes was also similar between groups. CONCLUSIONS: This study shows that the entire IA is not superior to the booklet/website alone, and that both are comparable in efficacy to the intervention arm of the SIMS-Trial. TRIAL REGISTRATION NUMBER: ISRCTN78940214.

Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Fluctuations of MS births and UV-light exposure.

BACKGROUND: Patients with multiple sclerosis (MS) are more frequently born in spring when compared to autumn. Fluctuation of UV-light has been hypothesized to drive this phenomenon. AIM: To assess the correlation between fluctuation of sunlight and birth season in persons with MS. METHODS: For this record-linkage study, we collected from the international MSBase and the Italian MS iMed-web databases the dates of birth of 11,415 patients with MS from 36 centres from 15 countries worldwide and compared these to dates of live-births from national registries. From all participating sites, we collected data on UV-light fluctuation and assessed its correlation with seasonal fluctuation in MS births. RESULTS: Compared with the reference cohort, an increased proportion of persons with MS were born in spring and a decreased proportion in autumn (odds ratio (OR) to be born in spring versus autumn = 1.158, χ² = 36.347, P < 0.001). There was no significantly increased fluctuation of MS births with increased quartile of ambient UV-light fluctuation (Ptrend = 0.086). CONCLUSION: Seasonal fluctuation of MS births as found in this worldwide cohort of patients with MS did not correlate with variation in seasonal fluctuation of UV-light. Most likely, it results from a complex interplay between fluctuation of sunlight, behavioural factors, other environmental factors and (epi)genetic factors.

Prevalence of 2-year "No evidence of disease activity" (NEDA-3 and NEDA-4) in relapsing-remitting multiple sclerosis. A real-world study.

BACKGROUND: No evidence of disease activity (NEDA) is becoming a gold standard in the evaluation of disease modifying therapies (DMT) in relapsing-remitting multiple sclerosis (RRMS). NEDA-3 status is the absence of relapses, new activity on brain MRI, and disability progression. NEDA-4 meets all NEDA-3 criteria plus lack of brain atrophy. OBJECTIVE: Aim of this study was to investigate the prevalence of two-year NEDA-3, NEDA-4, six-month delayed NEDA-3 (6mdNEDA-3), and six-month delayed NEDA-4 (6mdNEDA-4) in a cohort of patients with RRMS. Six-month delayed measures were introduced to consider latency of action of drugs. METHODS: Observational retrospective monocentric study. All the patients with RRMS starting DMT between 2015 and 2018, and with 2-year of follow-up, were included. Annualized brain volume loss (a-BVL) was calculated by SIENA software. RESULTS: We included 108 patients, the majority treated with first line DMT. At 2-year follow-up, 35 % of patients were NEDA-3 (50 % 6mdNEDA-3), and 17 % NEDA-4 (28 % 6mdNEDA-4). Loss of NEDA-3 status was mainly driven by MRI activity (70 %), followed by relapses (56 %), and only minimally by disability progression (7 %). CONCLUSION: In our cohort 2-year NEDA status, especially including lack of brain atrophy, was hard to achieve. Further studies are needed to establish the prognostic value of NEDA-3 and NEDA4 in the long-term follow-up.

Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study.

BACKGROUND: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). METHODS: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. RESULTS: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). CONCLUSIONS: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

An information aid for newly diagnosed multiple sclerosis patients improves disease knowledge and satisfaction with care.

BACKGROUND: Patients report information deficits in the period surrounding diagnosis of multiple sclerosis (MS). We assessed the effectiveness of an add-on information aid for newly diagnosed MS patients. METHODS: We randomly assigned 120 newly diagnosed MS patients from five Italian centres to diagnosis disclosure (current practice at the centre) or current practice plus information aid (ISRCTN81072971). The information aid consisted of a personal interview with a physician using a navigable compact disc and a take-home booklet. The primary composite endpoint was score in the highest tertile of MS knowledge and satisfaction with care questionnaires. Other endpoints were safety; treatment adherence; extra contacts/consultations; switching of care centre; and changes in Hospital Anxiety and Depression Scale and Control Preference Scale scores. RESULTS: At 1 month, 30/60 intervention and 8/60 control patients achieved the primary endpoint (odds ratio [OR] 6.5, 95% CI 2.6-16.0; p < 0.001; number needed to treat [NNT] 3). Figures at 6 months were 26/60 intervention and 11/60 control patients (OR 3.4, 95% CI 1.5-7.8; p = 0.04; NNT 4). There were no adverse events. No significant treatment effects were seen on secondary outcomes. CONCLUSION: The information aid was safe and significantly associated with attainment of the primary outcome at 1 and 6 months.

The Multiple Sclerosis Knowledge Questionnaire: a self-administered instrument for recently diagnosed patients.

There are few studies on patient knowledge in multiple sclerosis (MS), and only two published questionnaires. The objective of this article was to develop and validate the MS Knowledge Questionnaire (MSKQ), a self-assessed instrument for newly diagnosed MS patients. Thirty multiple-choice statements, conceived to test MS knowledge, were produced by a multidisciplinary panel and pre-tested on three MS patients, resulting in an intermediate 26-item version. This was tested on 54 MS patients for internal consistency, content and construct validity (validation sample I). The final (25-item) MSKQ was a primary outcome measure in the SIMS-Trial on an information aid to newly diagnosed MS patients. Postal responses of SIMS-Trial participants to the MSKQ a month after intervention (validation sample II) were analysed. Median MSKQ scores in validation samples I and II were, respectively, 18 (range 9-23) and 17 (range 3-24). Acceptability, internal consistency (Kuder-Richardson-20 formula 0.76) and content validity were good. Educational attainment and receiving the information aid were the main independent predictors of MS knowledge. Other predictors were female sex (positive association) and disease duration (negative association). In conclusion, the MSKQ has good clinimetric properties and is sensitive to an educational intervention. We propose the MSKQ as a brief instrument for clinical practice and research.

The contribution of enhancing lesions in monitoring multiple sclerosis treatment: is gadolinium always necessary?

BACKGROUND: MRI is highly sensitive for monitoring of disease activity and treatment efficacy in MS. Patients treated with disease modifying therapy (DMT), who experience MRI activity, including contrast-enhancing lesions (CEL) or new/enlarged T2 lesions, should be evaluated for a switch to more effective treatment. Due to recent evidence of gadolinium (Gd) accumulation in the brain after repeated administration of Gd-based contrast agents, FDA recommended to limit its use. AIM: To investigate the proportion of cases in which MRI activity would be detectable only using contrast-enhanced T1-weighted sequences.Secondary aims were to assess the presence of clinical or demographic variables associated with reactivation of pre-existing lesions and to analyse therapeutic consequences of different types of MRI lesions. METHODS: We retrospectively evaluated brain MRI scans, performed between 2014 and 2018, in patients treated with DMT for at least 6 months. RESULTS: We analysed 906 scans in 255 patients. New/enlarged T2 lesions were detected in 13.7% of cases, CEL in 3.5%, CEL without new T2 lesions (old lesions reactivated) in 1.1%. No variables were associated with old lesions reactivated. CEL with T2 equivalent were at higher risk of DMT switch, compared with new/enlarged T2 lesions without corresponding CEL (OR 4.0, 95% CI 1.5-10.4, p  = 0.005). CONCLUSIONS: Reactivation of pre-existing lesions is limited to a tiny fraction of MRI studies. Gd + T1-weighted images could be omitted, in patients treated with DMT for at least 6 months, without relevant loss of information.

Long-term cryostorage does not adversely affect the outcome of oocyte thawing cycles.

This multi-centre study evaluated systematically the influence of the duration of cryostorage on the outcome of thawing cycles when using slow-frozen oocytes. The thawing cycles were retrospectively divided into three main groups based on cryostorage duration: group A, 1-3 months; group B, 4-6 months; and group C, 7-48 months. Group C was subsequently divided into three subgroups: group C1, 7-9 months; group C2, 10-12 months; and group C3, 13-48 months. Main outcome measures observed were oocyte survival after thawing, fertilization, cleavage; embryo quality and development, implantation, and birth. No significant differences in main outcome measures were observed between all the groups studied. In conclusion, human oocytes can be safely cryostored for several years. This finding could encourage the wider use of oocyte cryopreservation as a clinical procedure in assisted reproduction.

Lamotrigine in the treatment of SUNCT syndrome.

Short-lasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is considered an intractable condition. The authors treated five patients with lamotrigine (125 to 200 mg daily), obtaining a complete remission in three patients and a substantial reduction (about 80%) of attack frequency in the other two. No adverse effects were noted.

Nocturnal eating syndrome in adults.

Ten adult subjects were referred to our sleep disorders center complaining of difficulty in maintaining sleep due to frequent and recurrent awakenings to eat or drink. All patients manifested more than one episode per night, characterized by compulsive food seeking and a return to sleep only after adequate food intake. Food-seeking drive was described as an urgent abnormal need to swallow food and was associated with an absence of real hunger. Six subjects showed an elective nighttime intake of carbohydrates, and in all cases only edible substances were injected. The patients were always fully awake during the episodes and could clearly recall them in the morning. Polysomnographic investigation showed low levels of sleep efficiency, a high number of awakenings and a strict relation between nocturnal eating episodes and nonrapid eye movement (NREM) sleep. The average length of each episode was 3.5 minutes. The "eating latency", that is the interval between awakening and chewing start, was shorter than 30 seconds in 50% of the episodes. No medical, hormonal or neurological disorders were found during clinical and laboratory investigations. Body mass index was abnormally high in six patients. Anorexia nervosa and bulimia were carefully excluded. Various psychiatric disturbances were found in nine subjects, who were nevertheless well-functioning adults. Concurrent dyssomniac disorders, such as narcolepsy or periodic leg movements occasionally associated with restless legs syndrome, were diagnosed in five patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Psychiatric comorbidity and psychosocial stress in patients with tension-type headache from headache centers in Italy. The Italian Collaborative Group for the Study of Psychopathological Factors in Primary Headaches.

A multicenter study was carried out in 10 Italian Headache Centers to investigate the prevalence of psychosocial stress and psychiatric disorders listed by the IHS classification as the "most likely causative factors" of tension-type headache (TTH). Two hundred and seventeen TTH adult outpatients consecutively recruited underwent a structured psychiatric interview (CIDI-c). The assessment of psychosocial stress events was carried out using an ad hoc questionnaire. The psychiatric disorders that we included in the three psychiatric items of the fourth digit of the IHS classification were depressive disorders for the item depression, anxiety disorders for the item anxiety, and somatoform disorders for the item headache as a delusion or an idea. Diagnoses were made according to DSM-III-R criteria. At least one psychosocial stress event or a psychiatric disorder was detected in 84.8% of the patients. Prevalence of psychiatric comorbidity was 52.5% for anxiety, 36.4% for depression, and 21.7% for headache as a delusion or an idea. Psychosocial stress was found in 29.5% of the patients and did not differ between patients with and without psychiatric comorbidity. Generalized anxiety disorder (83.3%) and dysthymia (45.6%) were the most frequent disorders within their respective psychiatric group. The high prevalence of psychiatric disorders observed in this wide sample of patients emphasizes the need for a systematic investigation of psychiatric comorbidity aimed at a more comprehensive and appropriate clinical management of TTH patients.

Chronic daily headache. How should it be included in the IHS classification?

A number of patients attending specialty headache centers complain of very frequent, almost continuous or continuous headaches, which are usually grouped together under the term chronic daily headache, a category which does not appear in the International Headache Society (IHS) classification. On the basis of the IHS criteria, these patients can only be classified as having a chronic tension-type headache with the possible addition of migraine, if migrainous attacks are superimposed on the "background" headache. However, several studies have demonstrated that most patients with chronic daily headache originally suffered from migraine and that their migraine has transformed, in the course of time, into a chronic headache picture in which isolated migraine attacks may or may not persist. Despite some differences in the personal opinions of authors involved in the care of patients with chronic daily headache, some views seem to be generally accepted: (1) the great majority of chronic daily headaches are transformations of an original episodic migraine and cannot be included in the chronic tension-type headache category, (2) the current IHS classification does not allow many patients presenting with chronic daily headache to be classified correctly, (3) an important nosological category (transformed migraine) has emerged from all the studies on this subject, (4) it is impossible to diagnose transformed migraine merely by "photographing" the picture of single attacks. Although some theoretical problems remain unresolved, it seems to us that the next revision of the IHS classification can no longer ignore the existence of chronic daily headache.

Characteristics of headache at menopause: a clinico-epidemiologic study.

The prevalence and characteristics of primary headaches in a large sample of postmenopausal women were investigated. Seventy-six out of 556 women (13.7%) were affected by headache of either the migraine or tension type. In 82% of cases onset had preceded the menopause. The postmenopausal course of headaches with a premenopausal onset differed according to type of headache and type of menopause. Indeed, while migraine improved in almost two-thirds of cases, tension-type headache worsened or did not change in 70% of cases. However, in women who had undergone surgical ovariectomy, the natural course of migraine was worse than in those who had a physiological menopause (P = 0.003). Among the symptoms covered by the Kuppermann Index, only anxiety and insomnia were correlated with headache. The favourable course of migraine in the postmenopausal period can be attributed primarily to the absence of variations in sex hormone levels although psychological factors also seem to play a fundamental role.

Course of primary headaches during hormone replacement therapy.

OBJECTIVE: The aim of the present study was to evaluate how hormone replacement therapy (HRT) could influence the course of primary headaches in postmenopausal women. METHODS: Fifty patients presenting for clinical evaluation of menopausal status and suffering from headache were enrolled. The observational period lasted 7 months during which women filled in a diary with the clinical characteristics of headache attacks (frequency, days with headache, severity) and the analgesic use (no. of analgesic/month). Climacteric symptoms and both anxiety and depression were also measured. At the first visit the patients were divided into two groups: those suffering from migraine without aura (MwA) and those suffering from episodic tension-type headache (ETTH) and separately randomized. After a month of run-in period, they received two different HRT regimen, either: (1) transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens 0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up evaluations were planned after 1, 3 and 6 months of treatment. RESULTS: While we did not observe any significance change regarding headache parameters in ETTH patients during both transdermal and oral treatment, the course of migraine was significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P < 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased during HRT in the subgroup assuming oral formulation. On the contrary, no changes in the same parameters were found in the group taking transdermal treatment. Moreover, while severity of migraine was unaffected by HRT, analgesic consumption was significantly increased in the subgroup on oral treatment (F = 6.3; P = 0.001). CONCLUSIONS: HRT significantly affects the course of headache in postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH remained stable throughout the observational period, patients suffering from MwA worsened their symptoms within the first 3 months of treatment. In particular, the oral route of administration significantly worsened migraine in comparison to the transdermal route.

Factors associated with pain complaints in a clinical sample of postmenopausal women.

The aims of this study were to evaluate the relationships occurring between pain complaints and postmenopausal status, and to look at the correlation between such complaints and other symptoms commonly related to the climacterium. A clinical sample of 99 consecutive postmenopausal patients requiring medical help were studied: 36 complained of muscle-skeletal pains whereas 33 presented with headache limiting daily activity. Climacteric syndrome, level of distress, coping style and bone mineral density were assessed with appropriate questionnaires and instruments. Neither bone mineral density, nor body mass index nor time since menopause were associated with either headaches or muscle-skeletal pains. According to the logistic regression being younger, being without a job, suffering from insomnia and having a lower ability in self-support by the means of comforting ideas predicts suffering from headache. A high level of distress and an avoidance behavior to problem facing predict the presence of pain complaints. In such cases the ineffectiveness of the coping mechanism (i.e. avoid the problem) could be the reason for the increased level of psychological distress. These findings indicate that complaining of pains or headache is not dependent upon postmenopausal status. Individual coping strategies and their effectiveness seem the main reasons for the presence of disabling musculoskeletal pains or headache.