Increase in migraine diagnoses and guideline-concordant treatment in veterans, 2004-2012.

Background and aim Health administrators, policy makers, and educators have attempted to increase guideline adherence of migraine medications while reducing inappropriate use of opioid- and barbiturate-containing medications. We evaluated the burden of migraine and proportion of guideline-concordant care in a large, national health care system over time. Methods We conducted a time-series study using data from the Veterans Health Administration (VHA) electronic health record. Veterans with migraines were identified by ICD-9 code (346.X). Prescriptions and comorbid conditions were evaluated before and after migraine diagnosis. Chi-square tests and logistic regression were performed. Results A total of 57,064 veterans were diagnosed with migraine headache (5.3%), with women significantly more likely diagnosed (11.6% vs. 4.4%, p < 0.0001). The number of veterans diagnosed with migraine has significantly increased over the years. By 2012, triptans were prescribed to 43% of people with migraine, with no difference by gender. However, triptan prescriptions increased from 2004 to 2012 in men, but not women, veterans. Preventive medicines showed a significant increase with the year of migraine diagnosis, after controlling for age, sex, race, and for comorbidities treated with medications used for migraine prevention. Conclusions The burden of migraines is increasing within the VHA, with a corresponding increase in the delivery of guideline-concordant acute and prophylactic migraine-specific medication.

Blood flow restriction augments the skeletal muscle response during very low-load resistance exercise to volitional failure.

The purpose of this study was to compare the acute muscular response with resistance exercise between the following conditions [labeled (% one-repetition maximum/% arterial occlusion pressure)]: high-load (70/0), very low-load (15/0), very low-load with moderate (15/40), and high (15/80) blood flow restriction pressures. Twenty-three participants completed four sets of unilateral knee extension to failure (up to 90 repetitions) with each condition, one condition per leg, each day. Muscle thickness and maximal voluntary contraction (MVC) were measured before (Pre), immediately after (Post-0), and 15 min after (Post-15) exercise and electromyography (EMG) amplitude during exercise. Pre to Post-0 muscle thickness changes in cm [95% CI] were greater with 15/40 [0.57 (0.41, 0.73)] and 15/80 [0.49 (0.35, 0.62)] compared to 70/0 [0.33 (0.25, 0.40)]. Pre to Post-0 MVC changes in Nm [95% CI] were higher with 15/40 [-127.0 (-162.1, -91.9)] and 15/80 [-133.6 (-162.8, -104.4)] compared to 70/0 [-48.4 (-70.1, -26.6)] and 15/0 [-98.4 (-121.9, -74.9)], which were also different. Over the first three repetitions, EMG increased across sets, whereas in the last three repetitions it did not. EMG was also different between conditions and was generally greater during 70/0. Repetitions decreased across sets reaching the lowest for 70/0, and for very low loads decreased with increased pressure. In trained participants exercising to failure, lower load and the application of restriction pressure augment changes in muscle thickness and torque. The EMG amplitude was augmented by load. Training studies should compare these conditions, as the results herein suggest some muscular adaptations may differ.

The affective and behavioral responses to repeated "strength snacks".

Background A training program consisting of only one-repetition maximum (1RM) training results in similar strength adaptations as traditional resistance exercise. However, little is known regarding the affective or behavioral responses to this type of training. Aim To examine the affective and behavioral response to either a traditional resistance exercise program or a biweekly 1RM-training program. Methods Participants were trained for 8 weeks (2× per week). The HYPER group completed four sets of 8-12 repetitions; the 1RM group (TEST) worked up to a single maximal repetition. Results The TEST group felt more revitalized and had an increase in positive engagement during their first visit, whereas the HYPER group showed an increase in feelings of physical exhaustion during their first and last visits. There were no pre to post differences for the change in behavior or self-efficacy between groups. Conclusion 1RM training appears to elicit a more favorable affective response, compared with HYPER training, which may ultimately improve adherence to resistance-type exercise.

Are higher blood flow restriction pressures more beneficial when lower loads are used?

The application of blood flow restriction during low-load resistance exercise has been shown to induce muscle growth with high or low restriction pressures, however, loads lower than 20% one-repetition maximum (1RM) remain unexplored. Fourteen trained individuals completed six elbow flexion protocols involving three different loads (10%, 15%, and 20% 1RM) each of which was performed with either a low (40% arterial occlusion) or high (80% arterial occlusion) pressure. Pre- and post-measurements of surface electromyography (sEMG), isometric torque, and muscle thickness were analyzed. An interaction was present for torque (p < 0.001) and muscle thickness (p < 0.001) illustrating that all increases in pressure and/or load resulted in a greater fatigue and muscle thickness. There was no interaction for sEMG (p = 0.832); however, there were main effects of condition (p = 0.002) and time (p = 0.019) illustrating greater sEMG in the 20% 1RM conditions. Higher blood flow restriction pressures may be more beneficial for muscle growth when very low loads are used.

The acute muscular response to two distinct blood flow restriction protocols.

The purpose of this study was to determine acute physiological and perceptual responses to two commonly implemented blood flow restriction protocols. Using a within-subject design, 15 participants (age ∼25) performed four sets of unilateral elbow flexion with each arm. One arm exercised using a 3-cm elastic cuff inflated to 160 mmHg, whereas the other arm exercised using a 5-cm nylon cuff inflated to 40% of the individual's arterial occlusion pressure. While both protocols elicited increases in acute muscle thickness [pre: 4.5 (0.2) cm, post: 5.0 (0.2) cm; p < 0.001] and electromyography amplitude [first 3 reps: 55 ( 5 ) %MVC; last 3 reps: 87 ( 10 ) %MVC], there were no differences between conditions. Both protocols produced decreases in post-exercise strength (pre: 70 Nm, post: 51 Nm; p < 0.001) with no difference between conditions. The nylon protocol resulted in more repetitions during sets 2 [13 ( 2 ) vs. 9 ( 4 ); p = 0.001] and 3 [10 ( 2 ) vs. 7 ( 4 ); p = 0.05], while producing lower levels of discomfort following each set (average 3 vs. 4; p < 0.05). In conclusion, both protocols produced similar acute responses thought to be important for promoting muscle growth. However, the use of arbitrary pressures may place some individuals under complete arterial occlusion which may increase the potential risk of an adverse event.

Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation.

Bis-indolyl-(seco)-1,2,9a-tetrahydrocyclopropa[c]benz[e]indol-4-on e compounds are synthetic analogues of CC-1065 that are highly cytotoxic toward a broad spectrum of tumor cell lines. One of these compounds, called DC1, was conjugated to antibodies via novel cleavable disulfide linkers. Conjugates of DC1 with murine mAbs anti-B4 and N901 directed against tumor-associated antigens CD19 and CD56, respectively, proved to be extremely potent and antigen selective in killing target cells in culture. DC1 conjugates with humanized versions of anti-B4 and N901 antibodies were also constructed and demonstrated to be as cytotoxic and selective as the respective murine antibody conjugates. The anti-B4-DC1 conjugate showed antitumor efficacy in an aggressive metastatic human B-cell lymphoma survival model in SCID mice and completely cured animals hearing large tumors. Anti-B4-DC1 was considerably more effective in this tumor model than doxorubicin, cyclophosphamide, etoposide, or vincristine at their maximum tolerated doses.

Merocyanine 540, a fluorescent probe sensitive to lipid packing.

Binding of the lipophilic probe merocyanine 540 to artificial bilayers was assessed by measuring the enhancement of fluorescence which results when dye enters the hydrophobic environment of the membrane. Titration of a constant amount of dye with increasing amounts of vesicles revealed that much more dye binds to multilamellar and 1000-A unilamellar vesicles which are in the fluid-phase state than to comparable vesicles which are in the gel-phase state. Incorporation of cholesterol into fluid-phase vesicles at levels of greater than 20 mol% reduced dye binding, whereas cholesterol had no effect at any concentration when incorporated into gel-phase vesicles. Sonicated 200--300-A unilamellar gel-phase vesicles, which because of their reduced radius of curvature resemble fluid-phase bilayers in their more widely spaced exterior leaflet lipids, bound more dye than 1000-A unilamellar gel-phase vesicles constructed from the same lipid. These results suggest that merocyanine 540 is able to sense the degree of lipid packing of bilayers and inserts preferentially into bilayers whose lipids are more widely spaced.

Placebos, active control groups, and the unpredictability paradox.

Randomized controlled trials often rely on placebo control groups to estimate treatment differences. Recently, the high frequency of negative trials and ethical concerns surrounding the use of placebos have brought the use of placebo control groups under increased scrutiny. Although many psychiatric researchers argue that placebo control groups should be replaced with active control groups, we argue that preferential use of active control groups will not reduce the number of negative trials. Rather, we suggest that some of the variation and contradiction in randomized controlled trial results arises from the clinical heterogeneity of patient characteristics, disease severity, comorbidity, and cotherapies. Further characterization of patient heterogeneity, through improved disease taxonomies, severity indices, and classification of comorbid diseases, will serve to reduce clinical heterogeneity among patients and reduce the number of negative trials produced by wide variation in treatment and control response rates.

Exploring the roles of men. Caring for demented relatives.

1. Men are under-represented among family members providing care to a demented relative. 2. Few differences were noted among the male caregivers: men with demented relatives at home spent more time daily on caregiving tasks although both groups of men tended to rely on others for the "hands-on" care needed; institutionalized demented relatives were rated as being more impaired than those at home; and men caring for relatives at home seemed determined to continue in their role. 3. It is possible that men find it more difficult to become caregivers because of lack of support from other family members, the impairment of the relative and the need for direct care, and men's lack of involvement in providing direct care. 4. Nurses involved in dementia care should offer instructional sessions aimed at men, provide assistance in working through emotional problems, and encourage their participation in future research on the male caregiving experience.

The HUSKY program: an opportunity to insure Connecticut's children.

Uninsured children in Connecticut represent a diverse group, and insuring them is a monumental task. In August 1997, President Clinton signed into law the Children's Health Insurance Program, which provides $47 billion in funds to states over the next 10 years to insure the nation's low-income children. Connecticut has been a leader in modeling the federal Children's Health Insurance Program into action. Connecticut's version of the program, Healthcare for UninSured Kids and Youth, (HUSKY), was enacted over the summer, and, to date, has enrolled over 4,000 children in the program. Connecticut's HUSKY program provides a timely opportunity for the state, as well as community health centers and other primary-care facilities, to reach those uninsured children in Connecticut's communities and move the children into the HUSKY program. In order to achieve this goal, innovative outreach strategies need to be designed that utilize cultural and community resources to locate and insure these children.

The role of gender in MPH graduates' salaries.

Several studies have demonstrated that workforce roles and salaries differ substantially between men and women in administrative positions within the health care industry. Recent studies of graduates with masters of business administration (MBA) and masters of health administration (MHA) degrees have indicated that women tend to experience lower salaries, given like responsibilities. However, the impact of gender on salary has been less studied among masters of public health (MPH) graduates in the health care field. Our objective was to assess the impact of gender on salary among MPH degree graduates. Using a cross-sectional survey of all graduates from the MPH program at Yale University between 1991-1997 (n = 201, response rate = 51%), we ascertained graduates' reported salary in the first job post-graduation and reported salary in their current position. Bivariate and multivariate analyses were used to assess the unadjusted and adjusted associations between gender and salary. Salaries in both the first job post-graduation and in the current job differed significantly by gender, with women earning less than men (p-values < .05). Moreover, these differences persisted after controlling for a set of human capital measures including pre-MPH work experience, age at graduation, years since graduation, area of specialization within the MPH degree, and type of work site (governmental or nonprofit versus for-profit). Unlike studies of MBA and MHA graduates, however, this study did not find evidence that the gender-related salary gap widened as the years since graduation increased, although the sample size did not allow comprehensive testing of this trend.

A qualitative study of state-level zoonotic disease surveillance in new England.

Zoonotic diseases are infectious diseases transmittable between animals and humans and outbreaks of these diseases in animals can signify that humans are also infected (or vice versa). Thus, communication between animal and human health agencies is critical for surveillance. Understanding how these agencies conduct surveillance and share information is important for the development of successful automated zoonotic monitoring systems. Individual interviews were conducted with 13 professionals who perform animal or human zoonotic disease surveillance in one of the New England states. Questions centred on existing surveillance methods, collaborations between animal and human health agencies, and technological and data needs. The results showed that agencies routinely communicate over suspected zoonotic disease cases, yet there are barriers preventing automated electronic linking of health data of animals and humans. These include technological barriers and barriers due to sensitivity and confidentiality of information. Addressing these will facilitate the development of electronic systems for integrating animal and human zoonotic disease surveillance data.

Enol-keto tautomerism of alpha-ketophosphonates.

A number of alpha-ketophosphonates have been prepared and their enol-keto tautomerism has been studied by means of proton and phosphorus NMR and infrared spectroscopy and the ferric chloride test. Aliphatic ketophosphonates exist largely in the keto tautomeric forms, with only a small amount of enol forms present. All the aromatic acylphosphonates studied, however, enolize extensively. An x-ray analysis confirmed enolization and E configuration as the only stereochemical isomer. Reaction of diazomethane with diethyl p-methoxyphenylacetyl phosphonate gave a mixture of O-methylation and carbene insertion products, whereas the same reaction with diethyl isobutyryl phosphonate gave only carbene insertion products.

Involvement of spectrin in the maintenance of phase-state asymmetry in the erythrocyte membrane.

The fluorescent probe merocyanine 540 does not stain the plasma membrane of normal human or murine erythrocytes, nor of genetically abnormal human spherocytic erythrocytes. It does, however, stain erythrocyte membranes in several systems in which the underlying spectrin network is altered or missing. Because of the greater affinity of merocyanine 540 for fluid--phase lipid bilayers, these results suggest that the external leaflet of erythrocyte membranes becomes more disordered upon alteration or loss of the internal spectrin network. Analysis of the transbilayer arrangement of membrane phospholipids by digestion with phospholipase A2 suggests that lipid compositional asymmetry of the erythrocyte membrane is responsible for a phase-state asymmetry between the two lipid leaflets, and that spectrin is required to maintain this asymmetry and the gel-like state of the external leaflet.

Eradication of large colon tumor xenografts by targeted delivery of maytansinoids.

The maytansinoid drug DM1 is 100- to 1000-fold more cytotoxic than anticancer drugs that are currently in clinical use. The immunoconjugate C242-DM1 was prepared by conjugating DM1 to the monoclonal antibody C242, which recognizes a mucin-type glycoprotein expressed to various extents by human colorectal cancers. C242-DM1 was found to be highly cytotoxic toward cultured colon cancer cells in an antigen-specific manner and showed remarkable antitumor efficacy in vivo. C242-DM1 cured mice bearing subcutaneous COLO 205 human colon tumor xenografts (tumor size at time of treatment 65-130 mm3), at doses that showed very little toxicity and were well below the maximum tolerated dose. C242-DM1 could even effect complete regressions or cures in animals with large (260- to 500-mm3) COLO 205 tumor xenografts. Further, C242-DM1 induced complete regressions of subcutaneous LoVo and HT-29 colon tumor xenografts that express the target antigen in a heterogeneous manner. C242-DM1 represents a new generation of immunoconjugates that may yet fulfill the promise of effective cancer therapy through antibody targeting of cytotoxic agents.