The SF-12 (Hebrew version) is a reliable and valid measure, particularly in a nondepressed population.

Although the use of chloroquine (C) and hydroxychloroquine (HC) in the treatment of malaria prophylaxis during pregnancy is probably safe, the use of much higher doses for treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis during pregnancy has been controversial. We analyzed the cases of 24 pregnant women with a total of 27 pregnancies who had taken these drugs during their first trimester of pregnancy. C and HC were given in 11 patients with SLE, three with rheumatoid arthritis, and four for malaria prophylaxis. Most of these women had already been on antimalarial drugs for 1 to 172 months prior to pregnancy (mean, 32.2 months). Of the 27 pregnancies, 14 resulted in normal full-term deliveries, six were aborted due to severe disease activity or social conditions, three were stillbirths, and four pregnancies resulted in spontaneous abortions. No congenital abnormalities were detected in the 14 live births at ages between 9 months and 19 years (mean, 5.3 years). All these children are physically and developmentally normal with no clinical evidence of eye or hearing defects. The seven pregnancies that were associated with fetal loss occurred particularly in patients who had active SLE, although stillbirth and spontaneous abortion occurred also in patients with rheumatoid arthritis and in two of the three patients who had been treated prophylactically for malaria. Although of the 215 reported pregnancies with C and HC exposure, including our study, only seven (3.3%) had congenital abnormalities, the risk associated with antimalarials may be cumulative and further studies are needed to elucidate the safety of this drug later in pregnancy.

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Fibromyalgia is characterized by widespread pain, fatigue, sleep disturbances and other symptoms, and has a substantial socioeconomic impact. Current biomedical and psychosocial treatments are unsatisfactory for many patients, and treatment progress has been hindered by the lack of a clear understanding of the pathogenesis of fibromyalgia. We present here a model of fibromyalgia that integrates current psychosocial and neurophysiological observations. We propose that an imbalance in emotion regulation, reflected by an overactive 'threat' system and underactive 'soothing' system, might keep the 'salience network' (also known as the midcingulo-insular network) in continuous alert mode, and this hyperactivation, in conjunction with other mechanisms, contributes to fibromyalgia. This proposed integrative model, which we term the Fibromyalgia: Imbalance of Threat and Soothing Systems (FITSS) model, should be viewed as a working hypothesis with limited supporting evidence available. We hope, however, that this model will shed new light on existing psychosocial and biological observations, and inspire future research to address the many gaps in our knowledge about fibromyalgia, ultimately stimulating the development of novel therapeutic interventions.Sections 'chronic primary pain', a new major category comprising five subtypes that reflect the distinct anatomical sites or body systems affected by pain 23 . Fibromyalgia belongs to the 'chronic widespread pain' subtype; the other four are complex regional pain syndrome, chronic primary headache or orofacial pain, chronic primary visceral pain, and chronic primary musculoskeletal pain.An even wider scope emerges when the broader overarching concept of central sensitivity syndromes is considered 24 . Central sensitivity syndromes comprise most COPCs as well as conditions not primarily typified by pain, such as periodic limb movement in sleep, multiple chemical sensitivity, female urethral syndrome and post-traumatic stress disorder 24 (see Fig. 2). All these conditions share evidence of central sensitivity and, to a lesser extent, similar neurotransmitter imbalance. They all show small-to-moderate response to serotoninnorepinephrine reuptake inhibitors and other centrally acting agents (for example, gabapentinoids) and little to no response to NSAIDs and opioids. These central sensitivity syndromes are frequently comorbid, are more common in women than in men, have a high prevalence of stress-related manifestations and psychopathology, and are associated with high sensitivity to daily and chronic stressors and increased sensitivity to everyday environmental sensory stimuli 24 .

Fibromyalgia is a common pain syndrome characterized by widespread pain, tenderness, and a number of other somatic symptoms and syndromes. Although there was original skepticism that any objective abnormalities would be identified in these individuals, at present there are many that have been reproducibly identified, and most point to dysregulation of central nervous system function as a key underlying pathogenic mechanism in this and related illnesses. This article reviews several objective abnormalities or measures that have been identified or used in fibromyalgia, and indicates which of these may be most promising to eventually use as biomarkers to follow the response to treatment or progress of disease over time.