A Preliminary Study of the Population-Adjusted Effectiveness of Substance Abuse Prevention Programming: Towards Making IOM Program Types Comparable

The Institute of Medicine distinguishes between programs based on who is targeted: the entire population (universal), those at risk (selective), or persons exhibiting the early stages of use or related problem behavior (indicated). Evaluations suggest that although universal programs can be effective in reducing and preventing substance use, selective and indicated programs are both more effective and have greater cost-benefit ratios. This paper tests these assumptions by comparing the impact of these program types in reducing and preventing substance use at the individual level (i.e., those exposed to intervention services) and in the population (i.e., those exposed and not exposed to intervention services). A meta-analysis was performed on 43 studies of 25 programs to examine program comparability across IOM categories. When examining unadjusted effect sizes at the individual level, universal programs were modestly more successful in reducing tobacco use, but selective and indicated programs were modestly more successful in reducing alcohol and marijuana use. When adjusted to the population level, the average effect sizes for selective and indicated programs were reduced by approximately half. At the population level, universal programs were more successful in reducing tobacco and marijuana use and selective and indicated programs were more successful in reducing alcohol use. Editors’ Strategic Implications: The authors’ focus on the public health value of a prevention strategy is compelling and provides a model for analyses of other strategies and content areas.     

Preoperative Chemotherapy for Colorectal Liver Metastases: Impact on Hepatic Histology and Postoperative Outcome

Some investigators have suggested that preoperative chemotherapy for hepatic colorectal metastases may cause hepatic injury and increase perioperative morbidity and mortality. The objective of the current study was to examine whether treatment with preoperative chemotherapy was associated with hepatic injury of the nontumorous liver and whether such injury, if present, was associated with increased morbidity or mortality after hepatic resection. Two-hundred and twelve eligible patients who underwent hepatic resection for colorectal liver metastases between January 1999 and December 2005 were identified. Data on demographics, clinicopathologic characteristics, and preoperative chemotherapy details were collected and analyzed. The majority of patients received preoperative chemotherapy (n = 153; 72.2%). Chemotherapy consisted of fluoropyrimidine-based regimens: 5-FU monotherapy, 31.6%; irinotecan, 25.9%; and oxaliplatin, 14.6%. Among those patients who received chemotherapy, the type of chemotherapy regimen predicted distinct patterns of liver injury. Oxaliplatin was associated with increased likelihood of grade 3 sinusoidal dilatation (p = 0.017). Steatosis >30% was associated with irinotecan (27.3%) compared with no chemotherapy, 5-FU monotherapy, and oxaliplatin (all p < 0.05). Irinotecan also was associated with steatohepatitis, as two of the three patients with steatohepatitis had received irinotecan preoperatively. Overall, the perioperative complication rate was similar between the no-chemotherapy group (30.5%) and the chemotherapy group (35.3%) (p = 0.79). Preoperative chemotherapy was also not associated with 60-day mortality. In patients with hepatic colorectal metastases, preoperative chemotherapy is associated with hepatic injury in about 20 to 30% of patients. Furthermore, the type of hepatic injury after preoperative chemotherapy was regimen-specific. Presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, March 11, Miami, Florida.     

Sildenafil Prevents Cardiovascular Changes after Bone Marrow Fat Embolization in Sheep

Background: Sudden, intraoperative cardiovascular deterioration as a result of pulmonary embolization of bone marrow fat is a potentially fatal complication during total hip and knee arthroplasty, intramedullary nailing, and spine surgery. Anesthetic management is challenging in the presence of increased right ventricular afterload due to pulmonary hypertension. Selective pulmonary vasodilation may be an appropriate prophylactic or therapeutic measure. The effect of sildenafil (phosphodiesterase inhibitor) on cardiovascular deterioration after bone marrow fat embolization was therefore investigated.

Methods: Bone cement (polymethylmethacrylate) was injected into three lumbar vertebrae in 12 sheep. Invasive blood pressures and heart rate were recorded continuously until 60 min after the last injection. Cardiac output and arterial and mixed venous blood gas variables were measured at selected time points. Before the first cement injection, 6 animals received a bolus injection (0.7 mg/kg) of sildenafil, with continuous infusion (0.2 mg [middle dot] kg-1 [middle dot] h-1) thereafter. Postmortem lung and kidney biopsies were taken for semiquantitative analysis of intravascular fat.

Results: Fat embolism was associated with a transient increase (21 +/- 7mmHg) in pulmonary arterial pressure. A transient decrease in arterial blood pressure and temporary increases in central venous pressure and dead space were also observed. No significant changes in any cardiovascular variable were observed after fat embolism in the sildenafil group. There was significantly (P < 0.05) less intravascular fat in the lungs of the sildenafil (median count of 5 emboli per microscopic view) compared with the control group (median count of 1).     

Community pharmacy services to optimise the use of medications for mental illness: a systematic review

The objective of this systematic review was to evaluate the impact of pharmacist delivered community-based services to optimise the use of medications for mental illness. Twenty-two controlled (randomised and non-randomised) studies of pharmacists' interventions in community and residential aged care settings identified in international scientific literature were included for review. Papers were assessed for study design, service recipient, country of origin, intervention type, number of participating pharmacists, methodological quality and outcome measurement. Three studies showed that pharmacists' medication counselling and treatment monitoring can improve adherence to antidepressant medications among those commencing treatment when calculated using an intention-to-treat analysis. Four trials demonstrated that pharmacist conducted medication reviews may reduce the number of potentially inappropriate medications prescribed to those at high risk of medication misadventure. The results of this review provide some evidence that pharmacists can contribute to optimising the use of medications for mental illness in the community setting. However, more well designed studies are needed to assess the impact of pharmacists as members of community mental health teams and as providers of comprehensive medicines information to people with schizophrenia and bipolar disorder     

How Should Functionally Equivalent Drugs be Reimbursed?

Statutory reimbursement agencies as well as private insurers throughout member states of the Organization for Economic Cooperation and Development (OECD) reimburse the cost of medicines on the basis of criteria that include robust clinical evidence, budget impact analysis, and incremental cost effectiveness. The Centers for Medicare and Medicaid Services (CMS) in the US are no exception to this rule and are, in principle, seeking to maximize benefit for their Medicare enrollees, whilst ensuring reasonable drug outlays for the small number of drugs that they reimburse. This paper provides a retrospective analysis of the way two functionally equivalent drugs are treated for reimbursement purposes by the CMS; the period under consideration was 2001–3. The two drugs, epoetin-α and darbepoetin-α, are used for the treatment of anemia in renal failure and in patients receiving chemotherapy. By reviewing the publicly available pharmacological and clinical data of epoetin-α and darbepoetin-α, the paper confirms the two drugs’ functional equivalence, despite their structural differences. The implications of dose conversion ratios and costs to Medicare are subsequently explored. It is argued that the issue of dose equivalence between epoetin-α and darbepoetin-α has significant implications for patients, practitioners, and payors. A payor’s perspective is adopted in this respect, whereby clinical evidence and pricing data are used simultaneously. Based on the clinical evidence, a dose conversion ratio for epoetin-α:darbepoetin-α is established, which achieves a comparable clinical effect for the two drugs and this is set to be <254IU:1μg. The incremental costs to Medicare are calculated subsequently. The Average Wholesale Price and the Outpatient Prospective Payment System rule that Medicare uses to reimburse providers are used and suggest that treatment of cancer patients with chemotherapy-related anemia with epoetin-α would save Medicare an estimated $US600 million each year. Patients would also benefit significantly in terms of lower co-payments for epoetin-α. The evidence is supportive of the decision made by the CMS to reimburse the two drugs at the rate reflecting the achievement of comparable clinical effects and therefore reducing the pass-through payments for darbepoetin-α to zero for the 2002–3 fiscal year.     

乳腺良恶性病变的磁共振T2*W首过灌注成像与血管生成相关性研究

Objective： To study the diagnostic value of T2^＊-weighted first-pass perfusion imaging in breast tumors. Methods： We analyzed the magnetic resonance imaging （MRI） information along with the pathological and immunohistochemistry results. Magnetic resonance imaging was performed in 28 patients with breast tumor. The time to signal intensity curves were generated according to the T2^＊-weighted first-pass perfusion imaging. The curve＇s maximal signal intensity drop rate and maximal signal intensity decrease time were analyzed and compared with the pathological diagnoses after surgery. Results： Malignant breast lesions showed higher maximal signal intensity drop rate （44.69% ± 17.07 vs. 17.22% ±7.49, P 〈 0.001） than benign lesions, but there was no significant difference of maximal signal decrease time between those two lesions （23.94 s ± 4.92 vs. 20.02 s ± 6.83, P 〉 0.05）. Conclusion： The T2^＊-weighted first-pass perfusion imaging has enough sensitivity and specificity in breast tumor diagnosis.     

Central Sensitization Theory of Migraine: Clinical Implications

The clinical science of migraine headache continues to evolve. Theories of the pathophysiology of migraine have progressed from the early vascular basis of migraine to more complex current theories that emphasize the centrality of neuronal dysfunction. The most recently articulated theory of migraine is the central sensitization hypothesis, which proposes that altered processing of sensory input in the brainstem, principally the trigeminal nucleus caudalis, could account for many of the temporal and symptomatic features of migraine, as well as its poor response to triptan therapy when such treatment is initiated hours after the onset of pain. Both preclinical and clinical data support the central sensitization theory. A critical clinical implication of this theory is that drugs that are capable of either aborting or arresting the process of central sensitization, most prominently dihydroergotamine, may have a unique role in the treatment of migraine. An additional, and highly practical, implication is based upon the finding that cutaneous allodynia—pain arising from innocuous stimulation of the skin, as in hair brushing or the application of cosmetics—is an easily identifiable marker of central sensitization. Thus, the presence or absence of cutaneous allodynia can be integrated into the routine clinical assessment of migraine and utilized as a determinant of treatment. Future basic and clinical research on central sensitization is likely to be of ongoing importance to the field.     

Changes in fetal presentation in twin pregnancies.

OBJECTIVE: The aim of the study was to describe the occurrence of spontaneous version in twins in the third trimester, as well as the correlation between antepartum and birth presentation. METHODS: Twin pregnancies were divided into four gestational age intervals: 20-23; 24-27; 28-31; and 32-36 weeks. Fetal presentation was categorized as cephalic (C) or non-cephalic (NC). Hospital records were reviewed to determine demographic factors, including mode of conception. Chi-square was used to compare distributions of presentations, and Cramer's V measure of association was used to correlate presentations in individual pregnancies between antepartum intervals and birth. RESULTS: A total of 207 pregnancies were included. The distribution of fetal presentations changed significantly through gestational age intervals (p < 0.001), although they were similar between 32-36 weeks and birth (p = 0.75). Correlation between antepartum and birth presentation in individual pregnancies strengthened throughout the four intervals. No correlation was seen between parity, gender, birthweight, or in vitro fertilization and fetal presentation or rate of spontaneous version.CONCLUSION: Many twins undergo spontaneous version in the third trimester, though there is excellent correlation between presentation at 32-36 weeks and birth. A cephalic presenting twin at > or = 28 weeks is highly likely to be in cephalic presentation at delivery.