The goal of this study was to estimate the effectiveness in actual clinical practice of recombinant human platelet-derived growth factor (rhPDGF) for the treatment of diabetic neuropathic foot ulcer (DNFU). Previously published pivotal trials have shown that by the 20th week of care 35 percent more ulcers healed in the group randomized to receive rhPDGF than those who did not receive rhPDGF (i.e., a relative risk [RR] of about 1.35). This represents an estimate of the efficacy of rhPDGF under the tightly controlled conditions of randomized clinical trials. Treatment effectiveness under standard clinical practice was estimated in a retrospective cohort study, controlling for treatment selection bias using propensity scores. We noted 24,898 individuals with a DNFU, of whom 9.6 percent received rhPDGF. We successfully created a propensity score model that evenly balanced many wound characteristics between those who received rhPDGF and those who did not. We created five groups, which varied from those least likely to receive rhPDGF to those most likely to receive rhPDGF. The RR, controlling for the propensity, to receive rhPDGF for a healed wound after treatment with rhPDGF as compared with standard care was 1.32 (1.22, 1.38). With respect to amputation, the RR for undergoing amputation after receiving rhPDGF was 0.65 (0.54, 0.78) as compared with those who did not receive rhPDGF. Within the limitations of our study, rhPDGF is more effective than standard therapy in both helping a wound to heal and preventing amputation, and its effect is similar to the efficacy estimates from previously published randomized controlled trials.

Diabetes is a common disease that is associated with numerous complications, including foot ulceration and amputation. In diabetic patients, the incidence of foot ulcers ranges from 1.0% to 4.1%, and the incidence of lower-extremity amputations ranges from 2.1 to 13.7 per 1000. Risk factors for developing foot ulcers and subsequent amputation include neuropathy, peripheral vascular disease, and trauma. To reduce these complications, several preventive strategies have been devised, from reducing risk factors to improving treatment and management.

Important lessons have been learned that have enhanced the safety and efficacy of injectable PLLA and have made it a desirable product for restoring facial volume.

Group II metabotropic glutamate receptors (mGluR2 and mGluR3) are implicated in schizophrenia. We characterized mGluR2, 3 in the human prefrontal cortex (PFC) and mesencephalon then compared cases with schizophrenia to matched controls. In the human brain, both receptors were expressed in the PFC and, unlike the rodent, in dopaminergic cell groups. In schizophrenia, we found significantly higher levels of mGluR2 mRNA in the PFC white matter. The expression of mGluR2, 3 in dopaminergic cells provides a mechanism for glutamate to modulate dopamine release in the human brain and this species-specific difference is critical to understanding rodent models in schizophrenia.

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