Footing the bill: the introduction of Medicare Benefits Schedule rebates for podiatry services in Australia

The introduction of Medicare Benefits Schedule items for allied health professionals in 2004 was a pivotal event in the public funding of non-medical primary care services. This commentary seeks to provide supplementary discussion of the article by Menz (Utilisation of podiatry services in Australia under the Medicare Enhanced Primary Care program, 2004-2008 Journal of Foot and Ankle Research 2009, 2: 30), by placing these findings within the context of the podiatry profession, clinical decision making and the broader health workforce and government policy.     

Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.     

Chemogenetic Inactivation of Dorsal Anterior Cingulate Cortex Neurons Disrupts Attentional Behavior in Mouse

Attention is disrupted commonly in psychiatric disorders, yet mechanistic insight remains limited. Deficits in this function are associated with dorsal anterior cingulate cortex (dACC) excitotoxic lesions and pharmacological disinhibition; however, a causal relationship has not been established at the cellular level. Moreover, this association has not yet been examined in a genetically tractable species such as mice. Here, we reveal that dACC neurons causally contribute to attention processing by combining a chemogenetic approach that reversibly suppresses neural activity with a translational, touchscreen-based attention task in mice. We virally expressed inhibitory hM4Di DREADD (designer receptor exclusively activated by a designer drug) in dACC neurons, and examined the effects of this inhibitory action with the attention-based five-choice serial reaction time task. DREADD inactivation of the dACC neurons during the task significantly increased omission and correct response latencies, indicating that the neuronal activities of dACC contribute to attention and processing speed. Selective inactivation of excitatory neurons in the dACC not only increased omission, but also decreased accuracy. The effect of inactivating dACC neurons was selective to attention as response control, motivation, and locomotion remain normal. This finding suggests that dACC excitatory neurons play a principal role in modulating attention to task-relevant stimuli. This study establishes a foundation to chemogenetically dissect specific cell-type and circuit mechanisms underlying attentional behaviors in a genetically tractable species.     

Reconsidering the family history in primary care

OBJECTIVE: The purpose of this paper is to review the role of the family history in predictive genetic testing, describe how family history taking is practiced in adult primary care, identify the current barriers to appropriate application of the family history, and outline the requirements for a new family history tool for primary care. DESIGN: We reviewed current perspectives on the family history, identifying key references in the medical literature and web-based family history tools through discussions with multiple content experts in clinical genetics, family medicine, and internal medicine. We conducted a Medline query using the search terms family history and primary care to identify references from the past 10 years. To illustrate the usefulness of family history information, we calculated the predictive value of family history and genetic information for familial adenomatous polyposis using current references and standard formulas. We identified paper and web-based family history tools through discussions with content experts. We also conducted a search on the World Wide Web to identify resources for electronic medical record and family history. RESULTS: The family history is the most important tool for diagnosis and risk assessment in medical genetics, and promises to serve as a critical element in the use of predictive genetic testing in primary care. Traditional medical education about family history has often been unsophisticated and use of family history in adult primary care has been limited, compounded by multiple substantive barriers. Although there are numerous paper and computer-based aides for taking the family history, none currently meets all the needs of adult primary care. CONCLUSIONS: The patient's family history remains a critical element in risk assessment for many conditions, but substantive barriers impede application in primary care practice, and evidence for its contribution to improved health outcomes is limited in this setting. Short of radical changes in reimbursement, new tools will be required to aid primary care physicians in the efficient collection and application of patient family history in the era of genetic testing.     

Limited number of immunoglobulin VH regions expressed in the mutant rabbit “Alicia”

A unique feature of rabbit Ig is the presence of V_H region allotypic specificities. In normal rabbits, more than 80% of circulating immunoglobulin molecules bear theV_Ha allotypic specificities, a1, a2 or a3; the remaining 10% to 20% of immunoglobulin molecules lack V_Ha allotypic specificities and are designated V_Ha^?. A mutant rabbit designated Alicia, in contrast, has predominantly serumimmunoglobulin molecules that lack the V_Ha allotypic specificities (Kelus and Weiss, Proc. Natl. Acad. Sci. USA 1986. 83: 4883). To study the nature and molecular complexity of V_Ha^? molecules, we cloned and determined the nucleotide sequence of seven cDNA prepared from splenic RNA of an Alicia rabbit. Six ofthe clones appeared to encode V_Ha^? molecules; the framework regions encoded by these clones were remarkably similar to each other, each having an unusual insertion of four amino acids at position 10. This insertion of four amino acids has beenseen in only 2 of 54 sequenced rabbit V_H genes. The similarity of the sequences of the six V_Ha^? clones to each other and their dissimilarity to most other V_H genes leads us to suggest that the V_Ha^? molecules in Alicia rabbits are derived predominantly from one or a small number of very similar V_H genes. Such preferential utilization of a small number of V_H genes may explain the allelic inheritance of V_H allotypes.