Excess risk of hip fractures attributable to the use of antidepressants in five European countries and the USA.

SUMMARY: The association between antidepressant use and hip fracture remains unclear. We conducted a systematic review to estimate Population Attributable Risks (PAR) for France, Germany, Italy, Spain, UK, and the USA. We report a heterogeneous prevalence of antidepressant use and related PARs, both lowest for Italy and highest for the USA. INTRODUCTION: Antidepressant use has been associated with an increased hip fracture risk in observational studies. However, the potential contribution of antidepressant consumption on the population rate of hip fractures has not been described. Our aim was to estimate the impact of the use of different classes of antidepressants on the rate of hip fracture at a population-level in France, Germany, Italy, Spain, the UK, and the USA. METHODS: We conducted a systematic literature review to estimate the pooled relative risk (RR) of hip fracture according to use of antidepressants. Prevalence rates of antidepressant use (Pe) in 2009 were calculated for each country using the The Intercontinental Medical Statistics database and three public databases from Denmark, the Netherlands, and Norway. Both the RR and Pe were used to calculate PAR of hip fractures associated with antidepressant use. RESULTS: The literature review showed an increased risk of hip fractures in antidepressant users (RR, 1.7; 95 % confidence interval (CI), 1.5-2.0). Rates of antidepressant use showed considerable differences between countries, ranging from 4.4 % (Italy) to 11.2 % (USA) in the year 2009. The estimated PAR of antidepressants on hip fracture rates were 3.0 % (95 % CI, 2.0-4.1; Italy), 3.1 % (95 % CI, 2.1-4.3; Germany), 3.8 % (95 % CI, 2.6-5.3; France), 4.8 % (95 % CI, 3.3-6.5; Spain), 4.9 % (95 % CI, 3.4-6.8; UK), and 7.2 % (95 % CI, 5.0-9.9; USA). PARs differed for different types of antidepressants, with highest attributable risks for selective serotonin reuptake inhibitors. CONCLUSIONS: These findings suggest that the potential contribution of antidepressant use to the population rate of hip fractures in the five large EU countries and the USA varies between 3 and 7 %.

Melanin-based color variation in response to changing climates in snakes.

Melanism, the process of heavier melanin deposition, can interact with climate variation at both micro and macro scales, ultimately influencing color evolution in organisms. While the ecological processes regulating melanin production in relation to climate have been extensively studied, intraspecific variations of melanism are seldom considered. Such scientific gap hampers our understanding of how species adapt to rapidly changing climates. For example, dark coloration may lead to higher heat absorption and be advantageous in cool climates, but also in hot environments as a UV or antimicrobial protection mechanism. To disentangle such opposing predictions, here we examined the effect of climate on shaping melanism variation in 150 barred grass snakes (Natrix helvetica) and 383 green whip snakes (Hierophis viridiflavus) across Italy. By utilizing melanistic morphs (charcoal and picturata in N. helvetica, charcoal and abundistic in H. viridiflavus) and compiling observations from 2002 to 2021, we predicted that charcoal morphs in H. viridiflavus would optimize heat absorption in cold environments, while offering protection from excessive UV radiation in N. helvetica within warm habitats; whereas picturata and abundistic morphs would thrive in humid environments, which naturally have a denser vegetation and wetter substrates producing darker ambient light, thus providing concealment advantages. While picturata and abundistic morphs did not align with our initial humidity expectations, the charcoal morph in N. helvetica is associated with UV environments, suggesting protection mechanisms against damaging solar radiation. H. viridiflavus is associated with high precipitations, which might offer antimicrobial protection. Overall, our results provide insights into the correlations between melanin-based color morphs and climate variables in snake populations. While suggestive of potential adaptive responses, future research should delve deeper into the underlying mechanisms regulating this relationship.

Potential impact of benzodiazepine use on the rate of hip fractures in five large European countries and the United States.

Benzodiazepine use increases the risk of falls and has been associated with an increased risk of hip fractures. Our aim was to estimate the possible population impact of the use of benzodiazepines on the rate of hip fracture in France, Germany, Italy, Spain, the United Kingdom, and the United States. We conducted a literature review to estimate the pooled relative risk (RR) for hip fractures and use of benzodiazepines. Prevalence rates of benzodiazepine use in 2009 were calculated for each country using the IMS MIDAS database and three public databases in Denmark, the Netherlands, and Norway. Both the RR and prevalence rates were used for calculation of population attributable risks (PARs) of hip fractures associated with benzodiazepine use. The literature review showed an increased risk of hip fractures in benzodiazepine users (RR = 1.4, 95 % CI 1.2-1.6). Rate of benzodiazepine use showed considerable differences between countries, ranging from 4.7 % to 22.3 % of population ever in a 1-year period. These are reflected in results for the PARs; estimated attributions of benzodiazepines to the rate of hip fractures were 1.8 %, 95 % CI 1.1-2.6 (Germany); 2.0 %, 95 % CI 1.2-2.8 (United Kingdom); 5.2 %, 95 % CI 3.2-7.3 (Italy); 7.4 %, 95 % CI 4.5-10.0 (France); 8.0 %, 95 % CI 4.9-11.0 (United States); and 8.2 %, 95 % CI 5.1-12.0 (Spain). PAR estimates suggest that the potential attribution of benzodiazepine use on the population rate of hip fractures in the five specified European countries and the United States varies between 1.8 % and 8.2 %. During the next phase of the IMI-PROTECT study, a comparison with individual patient data will show whether this approach is valid.

Ectopic ossification in the scar tissue of rats with myocardial infarction.

We describe the occurrence of bone-like formations in the left ventricular wall of infarcted rats treated or not with bone marrow cells injected systemically or locally into the myocardium. The incidence of ectopic calcification in hearts has been reported in rare cases in children with infarcts without previous coronary artery disease. Recently, ventricular calcification has been correlated with unselected bone marrow cell transplantation into infarcted rat hearts. Echocardiographic analysis of large infarction in rats frequently reveals the presence of echogenic structures in the left ventricular wall, sometimes projecting to the lumen of the chamber. The histological examination of these echogenic structures exhibited bone, cartilage, and marrow-like formations extending from the collagen-rich matrix of the ventricle wall. Microanalytical techniques verified the presence of hydroxyapatite in the mineral phase. Ossification was found in 25 out of 30 hearts evaluated 90 days postinfarct, being observed in 14 out of 17 animals submitted to cell therapy and in 11 out of 13 infarcted rats not submitted to cell therapy. Our study indicates that chondro-osteogenic differentiation can take place in the pathological rat heart independent of animal treatment with marrow cells.

Rituximab in refractory autoimmune diseases: Brazilian experience with 29 patients (2002-2004).

OBJECTIVE: Rituximab, a monoclonal antibody against B-lymphocytes that express CD 20, is already available for the treatment of non-Hodgkin's lymphoma. Due to the increased relevance of B-cell regulation in the pathogenesis of autoimmune diseases, rituximab is being used in the treatment of patients whose condition is refractory to conventional therapy. METHODS: We retrospectively evaluated the short-term efficacy and tolerance of rituximab in patients with various autoimmune diseases who were treated at the Hospital Israelita Albert Einstein in the city of Sao Paulo. RESULTS: During the period 2002-2004, 29 patients with various autoimmune diseases were treated with rituximab 375 mg/m2 for 4 consecutive weeks, or two doses of 1 g 2 weeks apart. We observed remarkable short-term results in all cases, except for one patient with thrombocytopenic purpura. Of note, we describe the results in two patients with diseases not previously treated with rituximab (hypergammaglobulinemic purpura of Waldenstrom and eosinophilic fasciitis with hypergammaglobulinemia). Treatment was well tolerated, with no unexpected adverse events. We also observed a marked reduction in steroid dosage. CONCLUSION: Rituximab seems to be safe and effective in the treatment of patients with a variety of autoimmune diseases that are refractory to other modalities of treatment.

Levodopa, melanoma, and Parkinson's disease.

Previous reports and the Physicians' Desk Reference caution against the use of levodopa in Parkinson's disease (PD) patients with melanoma. A critical review of the literature reveals only anecdotal evidence to support a link between levodopa and melanoma. In fact, levodopa has an antitumor effect on melanoma. We report nine patients with PD and melanoma who were treated with levodopa/carbidopa (L/C). Current evidence suggests that L/C can be used safely in PD patients with a history of melanoma.

Subchondral bone infractions in acute ligamentous knee injuries demonstrated on bone scintigraphy and magnetic resonance imaging.

Bone scintigraphy is used to detect radiographically silent fractures. Magnetic resonance imaging (MRI) is currently used to screen knee injuries for cartilage and ligament damage. MRI also delineates bone marrow and fractures. We investigated the bone scintigraphic findings in patients who had subchondral bone injuries demonstrated on MRI. Thirteen patients underwent MRI, three-phase bone scintigraphy with SPECT, and arthroscopic surgery after sustaining acute traumatic hemarthrosis of a knee. They all had clinically unsuspected subchondral bone injuries demonstrated on MRI with normal radiographs and normal overlying articular cartilage at arthroscopy, consistent with occult fractures. All showed focal bone repair on scintigraphy. Two of the 13 patients showed additional bone injuries only on bone scan. Two other patients scintigraphically showed focal bone repair at the medial femoral condyle due to avulsion of the medial collateral ligament. SPECT was easier to interpret than multi-view planar imaging. Bone scintigraphy confirms subchondral fractures demonstrated on MRI but also demonstrates ligament avulsion injuries and additional more subtle bone injuries.

Nail fold capillaroscopy: normal findings in children and adolescents.

OBJECTIVES: Capillaroscopy is a simple diagnostic method that permits noninvasive in vivo study of the capillary network. Studies designed to standardize capillary normality in children are limited. This article presents the capillaroscopic findings in healthy children and adolescents, thus making the application of this methodology viable for patients in this age range. MATERIAL AND METHODS: Healthy children were recruited from a private elementary school and junior high school. Nail fold capillaroscopy was performed using a stereomicroscope at 16 times magnification, addressing the following parameters: capillary morphology, capillary enlargement, devascularization, microhemorrhage, and subpapillary venous plexus visibility (PVS). These parameters were related to age, sex, ethnicity, and local periungal conditions. RESULTS: The sample comprised 329 individuals with mean age of 8.2 years. We observed atypical capillary morphology in 118 of the studied cases (36%), mainly bizarre capillaries in 90 (27%), meandering capillaries in 32 (10%), and bushy capillaries in 20 (6%). The enlarged capillary phenomenon was uncommon, being observed in 30 cases (9%). The number of capillaries per millimeter varied from five to nine. Deletion areas were detected in only seven individuals (2%). The subpapillary venous plexus was not visualized in 13 (4%) cases. Younger children presented higher PVS scores and fewer capillaries/mm as compared with older children. PVS scores were lower in males and in nonwhite children. Other variables were not associated with sex or ethnicity. CONCLUSIONS: The normal nail fold capillary network in children resembles that observed in adults with some differences, such as a lower number of loops per millimeter, a higher PVS score, and a higher frequency of atypical loops. This information is important for the diagnostic evaluation of children in the context of autoimmune rheumatic diseases.

I am not an animal: mortality salience, disgust, and the denial of human creatureliness.

The present research investigated the need to distinguish humans from animals and tested the hypothesis derived from terror management theory that this need stems in part from existential mortality concerns. Specifically, the authors suggest that being an animal is threatening because it reminds people of their vulnerability to death; therefore, reminding people of their mortality was hypothesized to increase the need to distance from animals. In support, Study 1 revealed that reminders of death led to an increased emotional reaction of disgust to body products and animals. Study 2 showed that compared to a control condition, mortality salience led to greater preference for an essay describing people as distinct from animals; and within the mortality salient condition but not the control condition, the essay emphasizing differences from other animals was preferred to the essay emphasizing similarities. The implications of these results for understanding why humans are so invested in beautifying their bodies and denying creaturely aspects of themselves are discussed.

Testosterone therapy and the pathogenesis of Kennedy's disease (X-linked bulbospinal muscular atrophy).

The mutation in X-linked bulbospinal muscular atrophy (XBSMA) is an increased CAG triplet repeat coding for a polyglutamine domain in the gene for the androgen receptor. This might impair the effect of testosterone on motor neurons, leading to their progressive degeneration. We report a trial of high-dose oral testosterone therapy in two brothers with XBSMA. Patient 1 received 37.5 mg of testosterone daily for more than 18 months, and Patient 2 received 25 mg per day for six months, both in combination with exercise therapy. Patient 1 showed improvement of up to 300% in muscle work output. Patient 2, who did less exercise, had no symptomatic improvement. These results indicate that exogenous testosterone therapy is not harmful, and may produce functional improvement when combined with exercise. We hypothesize that high-dose testosterone may reduce a toxic gain of function that the mutation produces, perhaps by inhibiting glutamate neurotoxicity.

Association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis in a child.

The authors report the case of a 15-year-old, HLA-B27-positive male patient who presented a rare association of ankylosing spondylitis, Crohn's disease and Takayasu's arteritis, which resulted in death. A brief review of the literature is provided.

Evaluation of the 1982 ARA lupus criteria data set in pediatric patients. Committees of Pediatric Rheumatology of the Brazilian Society of Pediatrics and the Brazilian Society of Rheumatology.

OBJECTIVE: Although commonly used, the 1982 revised criteria for the classification of Systemic Lupus Erythematosus (SLE) have not been completely evaluated in pediatric patients. This study was aimed at evaluating the sensitivity and specificity of the 1982 revised criteria when applied to pediatric patients. METHODS: One hundred and three children with SLE and 101 children with other rheumatic diseases were selected from 5 rheumatology centers in Brazil. Diagnosis of SLE by the 1982 criteria were compared with our clinical diagnosis. The diagnosis of other diseases was made according to internationally accepted classification criteria or, when these were not available, according to the physician's own experienced judgement. RESULTS: The median number of criteria fulfilled by the patients with SLE and the controls were 6 and 1, respectively. The most common criteria observed in children with SLE were: abnormal antinuclear antibody titers (94%), arthritis (83%), immunologic disorder (83%), hematologic disorder (70%), malar rash (67%), and photosensitivity (58%). When the immunologic disorder was broken down into its constituent elements, antibodies to dsDNA and Sm were observed in 73.0% (65/89) and 31.4% (15/48), respectively. The sensitivity and specificity observed were 96% and 100%, respectively. CONCLUSION: The 1982 classification criteria can be successfully applied to children with SLE. These criteria may serve as a basis for multi-center collaborative studies on children with SLE.

Death, sex, love, and neuroticism: why is sex such a problem?

Terror management theory posits that sex is a ubiquitous human problem because the creaturely aspects of sex make apparent our animal nature, which reminds us of our vulnerability and mortality. People minimize this threat by investing in the symbolic meaning offered by the cultural worldview. Because people high in neuroticism have difficulty finding or sustaining meaning, sex is a particular problem for them. In Study 1, mortality salience caused high-neuroticism participants to find the physical aspects of sex less appealing. Study 2 revealed that for such individuals thoughts of physical sex increase the accessibility of death-related thoughts. This finding was replicated in Study 3, which also showed that providing meaning by associating sex with love reduces the accessibility of death-related thoughts in response to thoughts of physical sex. These findings provide insight into why people high in neuroticism have conflicting thoughts about sexuality and why sexuality is so often regulated and romanticized.

The body as a source of self-esteem: the effect of mortality salience on identification with one's body, interest in sex, and appearance monitoring.

The present research investigated the role of the physical body as a source of self-esteem and tested the hypothesis derived from terror management theory that reminding people of their mortality increases self-esteem striving in the form of identification with one's body, interest in sex, and appearance monitoring. The results revealed that individuals high in body esteem responded to mortality salience manipulations with increased identification with their physical bodies in Study 1 and with increased interest in sex in Study 2. Study 3 showed that reminders of death led to decreased appearance monitoring among appearance-oriented participants who were low in body esteem. These findings provide insight into why people often go to extreme lengths to meet cultural standards for the body and its appearance.

Symptomatic cardiac involvement in juvenile rheumatoid arthritis.

In a retrospective study of 172 patients with juvenile rheumatoid arthritis, symptomatic cardiac involvement occurred in 13 (7.6%) patients (11 systemic and 2 polyarticular). There was predominance of the male sex and in most patients the involvement occurred in the initial years of the disease. Pericarditis occurred in seven patients; perimyocarditis in four and myocarditis in two patients. In the follow-up, one of the patients with pericarditis died of an arrhythmia during pericardiocentesis for cardiac tamponade. Among the patients with myocarditis, three died of septicemia during active disease. One of these three patients had myocarditis associated with cardiac tamponade. Among the 172 patients with juvenile rheumatoid arthritis, five children died; four belonged to the symptomatic cardiac involvement group (P less than 0.001). Cardiac involvement, in particular myocarditis and cardiac tamponade, can be regarded as a factor of worse prognosis.

Parental drug use and the socialization of AIDS knowledge and attitudes in children.

Children aged 6 to 18 who had a parent enrolled in drug treatment were matched on the child's age, sex, and ethnicity and on the parent's level of education with children from a community sample. They were compared with respect to parents' knowledge of HIV transmission, parents' efforts to teach their children (ages 6 to 18) about HIV and AIDS, and children's knowledge and attitudes regarding AIDS. Children of drug-abusing parents had more direct and indirect experience with people affected by AIDS than other children, and they demonstrated more knowledge of HIV transmission, once other variables were controlled. Overall, however, few group differences in parents' knowledge and socialization efforts or in children's AIDS-related knowledge and attitudes were observed. Although children of drug abusers appear to be learning as much as other children about HIV and AIDS, they nonetheless deserve special attention as a group at risk for HIV infection.

Human papillomavirus expression and p53 gene mutations in squamous cell carcinoma.

OBJECTIVES: To determine the incidence of human papillomavirus (HPV) infection and p53 gene mutation expression in squamous cell carcinomas (SCCs) of the oral cavity and tonsils, to correlate the presence of HPV and p53 gene mutation with known clinical and pathological features of SCC, and to determine whether infection with HPV or the presence of p53 gene mutations are independent prognosticators of patient survival. DESIGN: To accomplish this goal, 58 patients with SCCs of the oral cavity and 42 patients with SCCs of the tonsils were randomly examined. The cases examined met the criteria of 5-year clinical follow-up, availability of complete staging information and treatment history, and the presence of paraffin-embedded tumor specimens. Immunohistochemical tests were performed to identify the mutant p53 protein. Human papillomavirus identification was accomplished with polymerase chain reaction, with confirmation via restriction fragment length polymorphisms. RESULTS: The incidence of p53 gene mutation expression for this series was 66%. Human papillomavirus infection was found in 11 patients (11%). There was a trend toward increased p53 gene mutation expression with advancing stage of tumor in the oral cavity cancer group, although this was less evident in the tonsil cancer population. The p53 gene mutation status was found not to correlate with the histological grade of the tumor, patient age or sex, recurrence rates, or survival status. Like p53 expression, there were no correlations found between the presence of HPV and age, sex, histological grade, or recurrence rates. However, a correlation did exist between HPV and survival status in the tonsil cancer group, with improved survival noted among patients with tonsil cancers infected with HPV compared with those not infected with HPV. A significant correlation existed with both p53 gene mutation status and HPV status with respect to alcohol and tobacco use. The presence of the p53 gene mutation positively correlated with increased tobacco and alcohol use, whereas infection with HPV predicted a significantly lower rate of alcohol and tobacco consumption. CONCLUSIONS: Human papillomavirus infection is an independent risk factor for the development of oral cavity and tonsil SCCs in those patients with a relatively low alcohol and tobacco use history. Conversely, there is a strong association between heavy alcohol and tobacco use and mutation of the p53 gene. Neither p53 gene mutation nor HPV infection serve as prognosticators of tumor behavior in SCCs of the oral cavity or tonsils, with the exception of improved survival noted among patients with tonsil cancers infected with HPV.

Serum penicillin concentrations after intramuscular administration of benzathine penicillin G in children with rheumatic fever and controls.

Serum and urine penicillin levels were determined in 11 children with rheumatic fever (RF) who were receiving benzathine penicillin G (BPG) prophylactically every 3 weeks and in 10 children without RF who received the drug for the treatment of other infections. The dose given was 600,000 units for children weighing less than 25 kg and 1,200,000 units for those with a weight above 25 kg. Blood and urine samples were collected from both groups before and on days 7, 14 and 21 after BPG administration. Our results showed that: minimum inhibitory concentrations (MICs) of BPG for group A beta-hemolytic streptococci were 0.02 IU/ml or 0.0125 microgram/ml; intramuscular BPG did not give adequate serum levels to block the growth of group A beta-hemolytic streptococci in approximately 24 and 62% of children included in the study on days 14 and 21 after its administration, respectively; BPG metabolism was similar in both groups and did not depend on the underlying disease; serum and urine levels did not vary according to sex and weight; and there was a small correlation between serum and urine levels.

Translation, adaptation and validation of the Roland-Morris questionnaire--Brazil Roland-Morris.

The purpose of the present study was to translate the Roland-Morris (RM) questionnaire into Brazilian-Portuguese and adapt and validate it. First 3 English teachers independently translated the original questionnaire into Brazilian-Portuguese and a consensus version was generated. Later, 3 other translators, blind to the original questionnaire, performed a back translation. This version was then compared with the original English questionnaire. Discrepancies were discussed and solved by a panel of 3 rheumatologists and the final Brazilian version was established (Brazil-RM). This version was then pretested on 30 chronic low back pain patients consecutively selected from the spine disorders outpatient clinic. In addition to the traditional clinical outcome measures, the Brazil-RM, a 6-point pain scale (from no pain to unbearable pain), and its numerical pain rating scale (PS) (0 to 5) and a visual analog scale (VAS) (0 to 10) were administered twice by one interviewer (1 week apart) and once by one independent interviewer. Spearman's correlation coefficient (SCC) and intraclass correlation coefficient (ICC) were computed to assess test-retest and interobserver reliability. Cross-sectional construct validity was evaluated using the SCC. In the pretesting session, all questions were well understood by the patients. The mean time of questionnaire administration was 4 min and 53 s. The SCC and ICC were 0.88 (P<0.01) and 0.94, respectively, for the test-retest reliability and 0.86 (P<0.01) and 0.95, respectively, for interobserver reliability. The correlation coefficient was 0.80 (P<0.01) between the PS and Brazil-RM score and 0.79 (P<0.01) between the VAS and Brazil-RM score. We conclude that the Brazil-RM was successfully translated and adapted for application to Brazilian patients, with satisfactory reliability and cross-sectional construct validity.