Estimated research and development costs of rotavirus vaccines

Diseases like rotavirus afflict both upper- and lower-income countries, but most serious illnesses and deaths occur among the latter. It is a vital public health issue that vaccines for these types of global diseases can recover research and development (R&D) costs from high-priced markets quickly so that manufacturers can offer affordable prices to lower-income nations. Cost recovery depends on how high R&D costs are, and this study attempts to replace high, unverified estimates with lower, more verifiable estimates for two new vaccines, RotaTeq (Merck) and Rotarix (GlaxoSmithKline or GSK), based on detailed searches of public information and follow-up interviews with senior informants. We also offer a new perspective on “cost of capital” as a claim for recovery from public bodies. Our estimates suggest that companies can recover all fixed costs quickly from affluent markets and thus can offer these vaccines to lower-income countries at prices they can afford. Better vaccines are a shared project between companies and public health agencies; greater transparency and consistency in reporting of R&D costs is needed so that fair prices can be established.     

Priming with a very low dose of DNA complexed with cationic block copolymers followed by protein boost elicits broad and long-lasting antigen-specific humoral and cellular responses in mice

Cationic block copolymers spontaneously assemble via electrostatic interactions with DNA molecules in aqueous solution giving rise to micellar structures that protect the DNA from enzymatic degradation both in vitro and in vivo. In addition, we have previously shown that they are safe, not immunogenic and greatly increased antigen-specific CTL responses following six intramuscular inoculations of a very low dose (1 μg) of the vaccine DNA as compared to naked DNA. Nevertheless, they failed to elicit detectable humoral responses against the antigen. To gain further insight in the potential application of this technology, here we show that a shorter immunization protocol based on two DNA intramuscular inoculations of 1 μg of DNA delivered by these copolymers and a protein boost elicits in mice broad (both humoral and cellular) and long-lasting responses and increases the antigen-specific Th1-type T cell responses and CTLs as compared to priming with naked DNA. These results indicate that cationic block copolymers represent a promising adjuvant and delivery technology for DNA vaccination strategies aimed at combating intracellular pathogens.     

Atrial premature complexes and heart rate have prognostic significance in 1-month atrial fibrillation recurrence after electrical cardioversion.

AIMS: The aim of this study was to investigate the significance of simple 24-h Holter (24H) data after electrical cardioversion (CV) for atrial fibrillation (AF) recurrence. METHODS: We prospectively studied 47 consecutive patients subjected to CV, who successfully converted to sinus rhythm. All underwent echocardiography and 24H after CV. AF recurrence was studied at 14 days and 1 month by second 24H or by interim report of AF. RESULTS: About 53.2% remained in sinus rhythm (group I) and the rest recurred to AF (group II). Group I had fewer atrial premature complexes per hour (APC/h) (P = 0.002) and lower maximum (max HR), average, and minimum heart rates compared with group II (all Ps < 0.05). The optimal value of APC/h and max HR with best sensitivity and specificity was 32 APC/h and 90 bpm, respectively. These findings were the predictors of AF recurrence [hazard ratio (HR) = 4.5 with 95% CI = 1.7-11.7 and HR = 4.3 with 95% CI = 1.7-10.9, respectively]. Patients with the combination of both predictors had greater HR of AF recurrence compared with those with < 32 APC/h and max HR < 90 bpm (HR = 8.8 with 95% CI = 2.5-31.4). CONCLUSION: Patients with frequent APC/h and high max HR are at high risk for 1-month AF recurrence after electrical CV.     

Inpatient mortality of hip fracture patients in the Veterans Health Administration.

Hip fractures among elderly people frequently result in permanent disabilities, nursing home placement, and death. The bulk of hip fracture research focuses on elderly women. Within the Veterans Health Administration (VHA), the majority of patients are men. There are no published national reports on hip fractures with large male samples, or on related inpatient mortality among veterans. This retrospective study of 13,546 veterans with hip fracture discharges from 1998-2002 found unadjusted mortality rates are higher in the VHA, compared with the general population. VHA patients tend to be older men in poor health who stay in the hospital longer Increased knowledge about the risks and outcomes associated with hip fractures in men could lead to improved primary and secondary injury-prevention programs. Rehabilitation nurses in acute care can be catalysts in proactively incorporating protective devices, screening for osteoporosis, and initiating lifestyle changes in their plans of care to optimize outcomes for hip fracture patients.     

A Complication of Stellate Ganglion Block?

Abstract: Stellate ganglion block is commonly used to treat the sympathetically maintained pain which may occur in one‐third of patients with complex regional pain syndrome type 1. A complication that followed a single block and presented a diagnostic dilemma for the ophthalmologist is reported.     

Health managers' attitudes toward robotics and artificial computer intelligence: An empirical investigation

An empirical investigation of the perceived role of robotics and artificial computer intelligence in the future of health care reveals factors favoring a positive attitude by health administrators. The study employed a two-part survey administered in late 1989 and early 1990 to health care managers in hospitals and nursing homes. Part One of the survey asked about the participant, his or her work habits and work environment. Part Two obtained a psychological profile of rationality vs. intuition in problem solving. Through bivariate and multivariate post hoc statistical tests, we discovered the following variables which significantly determined attitudes toward robotics and artificial computer intelligence: sex, number of employees supervised; perceptions of waste and inefficiency in the workplace; perceptions of time-consuming personnel problem; perceived need to make more efficient use of time, money, and facilities; and perceived favorable climate for innovation. Among the factors which did not have an effect on attitudes toward advanced technology were three measures of rationality vs. intuition in problem solving.     

Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors.

CYP51 fulfills an essential requirement for all cells, by catalyzing three sequential mono-oxidations within the cholesterol biosynthesis cascade. Inhibition of fungal CYP51 is used as a therapy for treating fungal infections, whereas inhibition of human CYP51 has been considered as a pharmacological approach to treat dyslipidemia and some forms of cancer. To predict the interaction of inhibitors with the active site of human CYP51, a three-dimensional quantitative structure-activity relationship model was constructed. This pharmacophore model of the common structural features of CYP51 inhibitors was built using the program Catalyst from multiple inhibitors (n = 26) of recombinant human CYP51-mediated lanosterol 14alpha-demethylation. The pharmacophore, which consisted of one hydrophobe, one hydrogen bond acceptor, and two ring aromatic features, demonstrated a high correlation between observed and predicted IC(50) values (r = 0.92). Validation of this pharmacophore was performed by predicting the IC(50) of a test set of commercially available (n = 19) and CP-320626-related (n = 48) CYP51 inhibitors. Using predictions below 10 microM as a cutoff indicative of active inhibitors, 16 of 19 commercially available inhibitors (84%) and 38 of 48 CP-320626-related inhibitors (79.2%) were predicted correctly. To better understand how inhibitors fit into the enzyme, potent CYP51 inhibitors were used to build a Cerius(2) receptor surface model representing the volume of the active site. This study has demonstrated the potential for ligand-based computational pharmacophore modeling of human CYP51 and enables a high-throughput screening system for drug discovery and data base mining.