Efficacy and safety of hydrokinesitherapy in patients with dystrophinopathy.

Duchenne muscular dystrophy (DMD) is one of the most common forms of hereditary muscular dystrophies in childhood and is characterized by steady progression and early disability. It is known that physical therapy can slow down the rate of progression of the disease. According to global recommendations, pool exercises, along with stretching, are preferable for children with DMD, as these types of activities have a balanced effect on skeletal muscles and allow simultaneous breathing exercises. The present study aimed to evaluate the effectiveness of regular pool exercises in patients with Duchenne muscular dystrophy who are capable of independent movement during 4 months of training. 28 patients with genetically confirmed Duchenne muscular dystrophy, who were aged 6.9 ± 0.2 years, were examined. A 6-min distance walking test and timed tests, namely, rising from the floor, 10-meter running, and stair climbing and descending, muscle strength of the upper and lower extremities were assessed on the baseline and during dynamic observation at 2 and 4 months. Hydrorehabilitation course lasted 4 months and was divided into two stages: preparatory and training (depend on individual functional heart reserve (IFHR)). Set of exercises included pool dynamic aerobic exercises. Quantitative muscle MRI of the pelvic girdle and thigh was performed six times: before training (further BT) and after training (further AT) during all course. According to the results of the study, a statistically significant improvement was identified in a 6-min walking test, with 462.7 ± 6.2 m on the baseline and 492.0 ± 6.4 m after 4 months (p < 0.001). The results from the timed functional tests were as follows: rising from the floor test, 4.5 ± 0.3 s on the baseline and 3.8 ± 0.2 s after 4 months (p < 0.001); 10 meter distance running test, 4.9 ± 0.1 s on the baseline and 4.3 ± 0.1 s after 4 months (p < 0.001); 4-stair climbing test, 3.7 ± 0.2 s on the baseline and 3.2 ± 0.2 s after 4 months (p < 0.001); and 4-stair descent test, 3.9 ± 0.1 s on the baseline and 3.2 ± 0.1 s after 4 months (p < 0.001). Skeletal muscle quantitative MRI was performed in the pelvis and the thighs in order to assess the impact of the procedures on the muscle structure. Muscle water T2, a biomarker of disease activity, did not show any change during the training period, suggesting the absence of deleterious effects and negative impact on disease activity. Thus, a set of dynamic aerobic exercises in water can be regarded as effective and safe for patients with DMD.

Racial and ethnic differences in perceptions of campus climate related to sexual violence.

Objective: To assess perceptions of university institutional climate related to sexual violence and whether these differed by race/ethnicity. Participants: Matriculated undergraduates > age 18 (n = 1028). Methods: Students were invited via campus email to participate in an online survey. Results: Overall, only 20% agreed that the university is creating an environment in which unwanted sexual experiences seemed common or normal, but these findings differed by race. Black students were more likely than their white peers to feel the university is creating an environment in which unwanted sexual experiences seem common or normal (37.3% vs. 19.7%, p < .001) and creating an environment in which such instances were more likely to occur (33.3% vs. 13.4%, p < .001). Conclusions: Data suggest that while students generally perceive that the university is working to create a positive and safe climate, these perceptions vary by race. Further investigation is necessary to better understand the concerns of students of color.

Transfusion-associated circulatory overload prevention: a retrospective observational study of diuretic use.

BACKGROUND AND OBJECTIVES: Approaches to preventing transfusion-associated circulatory overload (TACO) include the use of diuretics. The purpose of this study was to determine how commonly diuretics are prescribed in patients receiving a red-blood-cell (RBC) transfusion. MATERIALS AND METHODS: This was a retrospective study of 200 adult inpatient RBC transfusion orders, 50 consecutive at each of four academic institutions. Only the first transfusion order for each patient was included. Only 1 or 2 unit orders were included. The primary outcome was the percentage of patients receiving furosemide peri-transfusion. Secondary objectives included the dose, route, and timing of furosemide and the association of clinical factors with ordering furosemide. RESULTS: The median age was 62·5 years (IQR 53, 73), and 52% were female. Peri-transfusion furosemide was ordered in 16% (95% CI 11-21%). The most common dose was 20 mg (55%), the route intravenous (90%) and timing post-transfusion (74%). At least one risk factor for TACO was present in 55% of patients: renal dysfunction (33%), older than 70 years (28%), history of congestive heart failure (18%), ejection fraction <60% (16%) and diastolic dysfunction (5%). Low haemoglobin as an indication for transfusion (OR 4·2; 95% CI 1·4-12·8) and diuretics on admission (OR 3·5; 95% CI 1·5-8·0) were associated with ordering furosemide peri-transfusion. CONCLUSIONS: Furosemide is not routinely ordered for RBC transfusion, even in patients with risk factors for TACO. Studies assessing the safety, efficacy, optimal dose, and timing of furosemide in preventing TACO are justified.

Audit of appropriate use of platelet transfusions: validation of adjudication criteria.

BACKGROUND AND OBJECTIVES: Platelet (PLT) transfusions must be used appropriately, as they are in chronic short supply, costly and risky to patients. The goals of this audit were to: (1) validate preset adjudication criteria through an audit of appropriateness at four large academic hospitals; (2) identify variability in appropriateness across medical services, physician specialties or hospital locations; and (3) inform logistical or educational interventions that may reduce inappropriate use. MATERIALS AND METHODS: A chart review of two hundred patients receiving PLT transfusions was performed. Fifty consecutive transfusion episodes per site were audited in detail. Each transfusion episode was independently adjudicated as appropriate or inappropriate by two transfusion specialists based on predetermined criteria. RESULTS: The adjudication criteria performed well with simple agreement of 95% (kappa statistic 0·83) between reviewers. Overall, 78% (95% CI: 72-84%) of PLT transfusions were adjudicated as appropriate, with results varying significantly by hospital site (range 62-94%). Prophylactic transfusions for non-bleeding patients had the highest proportion of appropriateness (85%, n = 80), and therapeutic transfusions for bleeding patients had the lowest (73%, n = 99). The lowest levels of appropriate platelet transfusions were observed in the operating rooms (60%) and when ordered by the general surgery service (55%). CONCLUSIONS: One in five platelet transfusions may be unnecessary, suggesting that interventions to improve PLT transfusion practice are warranted.

Reactivity to unpredictable threat as a treatment target for fear-based anxiety disorders.

BACKGROUND: Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT). METHODS: Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding. RESULTS: Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable. CONCLUSIONS: Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.

The association of fever with transfusion-associated circulatory overload.

BACKGROUND: Fever is described in transfusion-associated circulatory overload (TACO), reflecting either comprehensive haemovigilance or an inflammatory pathobiology (such as congestion-associated atheroma disruptions). METHODS: Hospital haemovigilance data (1/1/2010-31/12/2012) were reviewed for TACO cases (frequency and mode of referral). TACO with or without fever (TACO+F/-F) was examined for its association with patient age (as a surrogate for atheroma burden) and product age (as a surrogate for storage-related pyrogens). Fever in allergic transfusion reactions was also compared. RESULTS: Of 972 reactions, 107 suspected cases of TACO (11%) were seen. TACO+F vs. TACO-F occurred in 42·1 vs. 57·9%, respectively. TACO+F cases were discovered in referrals to investigate either a fever (in 47·1%) or dyspnoea (in 52·9%). Among TACO+F cases, 24·4% had already been febrile, whereas 75·6% exhibited a new reaction-associated fever. After excluding preexisting fevers, TACO+F occurred in 31·8% of TACO, compared with 8·2% of allergic reactions with fever, for an odds ratio of 5·2 (2·9-9·4 [95% CI]), P < 0·001. TACO+F/TACO-F showed no difference in median host age (69 vs. 64 years, P = 0·3), RBC age (22 days +F/-F, P = 0·9) or severity. CONCLUSION: Transfusion-associated circulatory overload disproportionately exhibits fever compared with allergic reactions. However, TACO+F did not associate with patient or product age, nor reflect severity. To better understand TACO+F, the fever-congestion sequence merits attention. Further study is needed to see whether TACO+F occurs as reproducibly elsewhere, and in association with atherosclerosis in a better characterized cohort.

Reactivity to uncertain threat as a familial vulnerability factor for alcohol use disorder.

BACKGROUND: When sober, problematic drinkers display exaggerated reactivity to threats that are uncertain (U-threat). Since this aversive affective state can be alleviated via acute alcohol intoxication, it has been posited that individuals who exhibit heightened reactivity to U-threat at baseline are motivated to use alcohol as a means of avoidance-based coping, setting the stage for excessive drinking. To date, however, no study has attempted to characterize the dispositional nature of exaggerated reactivity to U-threat and test whether it is a vulnerability factor or exclusively a disease marker of problematic alcohol use. METHOD: The current investigation utilized a family study design to address these gaps by examining whether (1) reactivity to U-threat is associated with risk for problematic alcohol use, defined by family history of alcohol use disorder (AUD) and (2) reactivity to U-threat is correlated amongst adult biological siblings. A total of 157 families, and 458 individuals, participated in the study and two biological siblings completed a threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Startle potentiation was collected as an index of aversive responding. RESULTS: Within biological siblings, startle potentiation to U-threat [intraclass correlation (ICC) = 0.35] and P-threat (ICC = 0.63) was significantly correlated. In addition, independent of an individuals' own AUD status, startle potentiation to U-threat, but not P-threat, was positively associated with risk for AUD (i.e. AUD family history). CONCLUSION: This suggests that heightened reactivity to U-threat may be a familial vulnerability factor for problematic drinking and a novel prevention target for AUD.

Anxiety-potentiated amygdala-medial frontal coupling and attentional control.

Anxiety disorders can be treated both pharmacologically and psychologically, but many individuals either fail to respond to treatment or relapse. Improving outcomes is difficult, in part because we have incomplete understanding of the neurobiological mechanisms underlying current treatments. In a sequence of studies, we have identified 'affective bias-related' amygdala-medial cortical coupling as a candidate substrate underlying adaptive anxiety (that is, anxiety elicited by threat of shock in healthy individuals) and shown that it is also chronically engaged in maladaptive anxiety disorders. We have provided evidence that this circuit can be modulated pharmacologically, but whether this mechanism can be shifted by simple psychological instruction is unknown. In this functional magnetic resonance imaging study, we extend a previously used translational anxiety induction (threat of shock) in healthy subjects (N=43) and cognitive task to include an element of instructed attentional control. Replicating our previous findings, we show that induced anxiety engages 'affective bias-related' amygdala-dorsal medial frontal coupling during the processing of emotional faces. By contrast, instructing subjects to attend to neutral shapes (and ignore faces) disengages this circuitry and increases putative 'attentional control-related' coupling between the amygdala and a more rostral prefrontal region. These neural coupling changes are accompanied by corresponding modulation of behavioural performance. Taken together, these findings serve to further highlight the potential role of amygdala-medial frontal coupling in the pathogenesis of anxiety and highlight a mechanism by which it can be modulated via psychological instructions. This, in turn, generates hypotheses for future work exploring the mechanisms underlying psychological therapeutic interventions for anxiety.

Consent for blood transfusion: do patients understand the risks and benefits?

BACKGROUND AND OBJECTIVES: Blood transfusion is a frequent medical intervention in hospitals. The benefits of, risks of and alternatives to blood transfusions are not consistently understood by patients. The objective of this study was to assess gaps in knowledge and comfort with the current process of consenting patients for blood transfusions. A standardised video regarding the risk and benefits of blood transfusions was developed and feedback regarding this tool was assessed. METHODS: After informed consent had been obtained, 25 patients receiving their first transfusion at a single academic centre were asked to complete a survey, watch a standardised educational video and complete a follow-up survey. RESULTS: The patient survey revealed that the information recollected from informed consent discussions was variable and incomplete. After the informed consent discussion, the majority of patients were comfortable with having a blood transfusion, although one-third did express concerns or worry about having a blood transfusion. After viewing the video, patients felt that the video improved their understanding of the risks (7·3 of 10), benefits (6·9 of 10) and alternatives (7·1 of 10) to transfusion, but it did not change their comfort with blood transfusion consent. CONCLUSION: Patients experienced a variable informed consent process prior to blood transfusion. Although the video improved their understanding of risks, it did not improve patient comfort towards giving consent for transfusion as the level of comfort was already high. The video is available online (http://www.youtube.com/watch?v=RxaPnLkgh-0) as an optional resource for patients (and physicians) who wish to receive standardised and accurate information about blood transfusions.

Diversity in auxology: between theory and practice. Proceedings of the 18th Aschauer Soiree, 13th November 2010.

Auxology has developed from mere describing child and adolescent growth into a vivid and interdisciplinary research area encompassing human biologists, physicians, social scientists, economists and biostatisticians. The meeting illustrated the diversity in auxology, with the various social, medical, biological and biostatistical aspects in studies on child growth and development.

Growth variation, final height and secular trend. Proceedings of the 17th Aschauer Soiree, 7th November 2009.

Growth and body height have always been topics interesting to the public. In particular, the stupendous increase of some 15-19cm in final adult height during the last 150 years in most European countries (the "secular trend"), the concomitant changes in body and head proportions, the tendency towards early onset of sexual maturation, the changes in the age when final height is being reached, and the very recent trend in body mass index, have generated much scientific literature. The marked plasticity of growth in height and weight over time causes problems. Child growth references differ between nations, they tend to quickly become out of date, and raise a number of questions regarding fitting methods, effects caused by selective drop-out, etc. New findings contradict common beliefs about the primary importance of nutritional and health related factors for secular changes in growth. There appears to be a broad age span from mid-childhood to early adolescence that is characterised by a peculiar insusceptibility. Environmental factors that are known to influence growth during this age span appear to have only little or no impact on final height. Major re-arrangements in height occur at an age when puberty has almost been completed and final height has almost been reached, implying that factors, which drive the secular trend in height, are limited to early childhood and late adolescence.

The role of taste and appetite regulation in the understanding of overweight and obesity. Proceedings of the 16th Aschauer Soiree, 26th April 2008.

Overweight and obesity have developed into major illnesses in most Western societies and significantly contribute to the financial burden of modern public health systems. Almost daily, new therapeutic proposals are published in the lay press, and also the scientific literature has increased dramatically in recent years. E.g., when searching MEDLINE (1966 - May 2008 (1)), the key word "obesity" meanwhile appears in more than 108,000 articles. Primary focus however, is put upon aspects of treatment, neglecting the role of taste and appetite regulation. Combining keywords like "obesity + treatment" results in over 50.000 citations, "obesity + diet" in over 23.000, "obesity + energy + expenditure" in over 13.000 citations (even "obesity + gastric + bypass" still evoke 2.600 citations), whereas "obesity + appetite + regulation" result in some 3.000, "obesity + NPY" - neuropeptid Y being one of the major chemical stimulators of appetite - evoke some 500 and "obesity + Arc + nucleus" - the arcuate nucleus being the anatomical centre of appetite regulation - no more than 370 scientific publications. The apparent scarcity of literature about taste and appetite regulation and the amazing lack of interest in neuronal information processing in overweight and obesity, has prompted the authors to brainstorm new aspects of the world-wide derailment of weight control.

IL-10 is not required to prevent immune hyperactivity during memory responses to Toxoplasma gondii.

Primary infection of IL-10 knockout (KO) mice with the protozoan parasite Toxoplasma gondii leads to a CD4(+)-T-cell dependent shock-like reaction with high systemic levels of IL-12 and IFN-gamma, severe liver pathology and death of mice. In the present study, this immune-mediated pathology was prevented by treatment of IL-10 KO mice with the anti-parasitic drug sulfadiazine, allowing these mice to progress to the chronic phase of infection. To address the role of endogenous IL-10 in the regulation of secondary immune responses to T. gondii, IL-10 KO mice were infected with the avirulent Me49 strain of this parasite, treated with sulfadiazine for 2 weeks starting at day 3 p.i., and were rechallenged 6 weeks p.i. with RH, a highly virulent strain of T. gondii. In these studies, chronically infected IL-10 KO mice survived secondary infection with RH and controlled parasite load. Although serum levels of IL-12 and IFN-gamma were higher in IL-10 KO mice than in wild type (WT) mice 8 days after RH rechallenge, these levels were well controlled in the absence of endogenous IL-10, suggesting that IL-10 is not required to down-regulate cytokine production during the memory response. Antigen-specific ex vivo recall responses further revealed that splenocytes from chronically infected WT and IL-10 KO mice responded to parasite antigen with similar production of IL-12 and IFN-gamma, and there was also no significant difference in ex vivo production of these cytokines by splenocytes in response to parasite antigen 7 days after secondary infection with T. gondii. Furthermore, IL-10 KO mice immunized with the Ts-4 vaccine-strain of T. gondii were protected when rechallenged with the virulent RH strain. Together, these studies demonstrate that the inhibitory effect of IL-10, which is required to prevent immune-mediated pathology during primary infection, is not required to prevent immune hyperactivity during a secondary response to T. gondii, and a highly effective memory response is generated in the absence of endogenous IL-10.

Early Start: an obstetric clinic-based, perinatal substance abuse intervention program.

Maternal substance abuse is a serious problem with significant adverse effects to mothers, fetuses, and children. The Early Start Program provides pregnant women in a managed care organization with screening and early identification of substance abuse problems, early intervention, ongoing counseling, and case management by a licensed clinical social worker located in the prenatal clinic, where she is an integral part of the prenatal team. We describe the development of the Early Start Program, its administrative history, and how it has interfaced with clinicians and administrators. We also highlight two important program characteristics: the partnership with a perinatal health services research unit and the degree to which the program could be "exported" to other managed care settings.

How "Caucasoids" got such big crania and why they shrank. From Morton to Rushton.

In the 19th century measurements of cranial capacity by Morton and others supported a "Caucasoid>Mongoloid>Negroid" hierarchy of intelligence. This continued through most of the 20th century but was challenged by a nonhierarchical view originating with Boas. Beginning in the 1980s Rushton correlated cranial and IQ measurements and presented a hierarchy with "Mongoloids" at the top. Each of these periods relates to its social context: the 19th-century hierarchy paralleled the height of European world domination; the nonhierarchy of the 20th century reflected world wars, worldwide depression, and the breakup of empires; the "Mongoloid>Caucasoid>Negroid" hierarchy followed the economic success of several Asian nations. Morton's cranial ranking was the result of his sampling error and his acceptance of the hierarchical thinking of his time. But how is it possible for Rushton to support the M>C>N ordering while using the data of several anthropologists who have rejected racial hierarchies on empirical grounds? The answer to this question involves a critique of Rushton's use of the race concept, his aggregation of diverse populations into three traditional races, his claim to explain differences in "cultural achievements" on the basis of variation in brain size, and a number of other problems. The study concludes by noting that the major consequence of these hierarchies is the apparent justification for the exploitation of those at the bottom.

Long-term outcomes of an abstinence-based, small-group pregnancy prevention program in New York City schools.

CONTEXT: Despite drops in U.S. teenage birthrates, questions continue to arise about how best to reduce the country's adolescent birthrate. School-based programs continue to be considered one of the best ways to reach adolescents at risk of early sexual activity. METHODS: A total of 312 students completed a pretest, a posttest and a follow-up one year after the posttest: 125 who had participated in a 3-4-month-long abstinence-based small-group intervention led by trained social workers, and 187 in a comparison group that received no special services. RESULTS: There were few significant differences between the intervention and comparison groups at posttest. At the one-year follow-up, however, intervention students had significantly better scores on locus of control, their relationship with their parents and (among males only) their attitudes about the appropriateness of teenage sex. Measures of depression, self-esteem, intentions to have sex, attitudes toward teenage pregnancy and various behaviors did not differ significantly between groups. By the time of the one-year follow-up, there was no difference between study groups among females in the initiation of sexual intercourse. Among the males, initiation of sexual intercourse appeared to be higher in the intervention group than in the comparison group, but the difference was not statistically significant. Positive outcomes were especially limited among students who were already sexually active at the start of the study, a finding that emphasizes the difficulties of reaching adolescents who are already at high risk for pregnancy CONCLUSIONS: A small-group abstinence-based intervention focusing on mental health can have some impact on adolescents' attitudes and relationships (particularly with their parents). Long-term evaluations are important for determining the effects of an intervention, as it is difficult to change adolescent risk behavior.