Levetiracetam dosing for seizure prophylaxis in neurocritical care patients.

BACKGROUND/OBJECTIVE: Levetiracetam is used for seizure prophylaxis in patients presenting with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). We aim to characterize the optimal levetiracetam dosage for seizure prophylaxis. METHODS: This retrospective cohort study included adult patients at an academic tertiary hospital presenting with SAH or TBI who received levetiracetam at a total daily dose (TDD) equivalent to or greater than 1000 mg. The primary outcome was combined seizure incidence, including clinical and subclinical seizures. RESULTS: We identified 139 patients (49.6% male, mean age 53 years) for inclusion. For patients receiving a 1000-mg TDD, the administration was 500 mg twice daily. For patients receiving >1000-mg TDD, 77/78 patients received 1000 mg twice daily and one patient received 750 mg twice daily. Patients receiving 1000-mg TDD had a higher seizure incidence than those receiving >1000-mg TDD (p = 0.01), despite no difference in examined confounders, including history of alcoholism (p = 0.49), benzodiazepine use (p = 0.28), or propofol use (p = 0.17). No difference in adverse effects was observed (anemia, p = 0.44; leukopenia, p = 0.60; thrombocytopenia, p = 0.86). CONCLUSIONS: Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing >1000-mg TDD.

A novel case of recurrent cylindroma of the orbit.

Cylindroma is a rare benign tumour of eccrine origin that has not been previously reported within the orbit. We report a case of a recurrent orbital cylindroma following incomplete excision. A 75-year-old female presented with a recurrent left inferomedial orbital mass. Seven years prior a mass of the same location was excised and on histology at the time resembled a cylindroma. The patient had a history of lung adenocarcinoma. Magnetic resonance imaging (MRI) found the recurrent mass to be a well-circumscribed lesion anterior to the inferior oblique. The mass was subsequently excised. Histological analysis found a well-circumscribed neoplasm with a characteristic jigsaw pattern of nested cells, consistent with cylindroma. This case demonstrates the possibility for cylindromas to occur within the orbit and their ability to reoccur if incompletely excised.

Inactivated Four-Factor Prothrombin Complex Concentrate Dosing Practices for Reversal of Warfarin-Related Intracranial Hemorrhage.

BACKGROUND/OBJECTIVE: Inactivated four-factor prothrombin complex concentrate (I4F-PCC, Kcentra®) has become an important agent for the urgent or emergent reversal of bleeding associated with vitamin K antagonists such as warfarin. There is recognized inter-institutional variability with the use of I4F-PCC, especially as it relates to dosing practices. We sought to characterize variations in I4F-PCC dosing practices and their impact on patient outcomes and describe overall real-world clinical practice surrounding I4F-PCC utilization in the context of the management of warfarin-related intracranial hemorrhage (ICH). METHODS: This is a multicenter retrospective pragmatic registry study of adult patients admitted at a participating study site between January 1, 2014, and December 31, 2015, who received I4F-PCC for reversal of warfarin-related ICH. Practices around warfarin-related ICH reversal in context of I4F-PCC utilization are described, including repeat I4F-PCC dosing, adjunctive reversal agents, and dose rounding policies (i.e., rounding doses to nearest vial size vs preparing exact/unrounded doses). All research was approved by local human investigation committees at each institution. RESULTS: Seventeen institutions contributed data on 528 patients to this registry. These institutions were primarily urban centers (74%), located in the southeast USA (47%), with Level 1 Trauma designation (79%), and with Comprehensive Stroke Center designation (74%). Most patients included in the study had sustained a non-traumatic ICH (68%), had a median admission GCS of 14 (IQR 7-15), and were receiving warfarin for atrial fibrillation (57.4%). There was substantial time latency between baseline INR and I4F-PCC (median 2.4 h, IQR 1.4-4.5 h). Most patients received adjunctive reversal agents, including vitamin K (89.5%) and fresh frozen plasma (FFP) (31.9%). A smaller proportion (6.0%) of patients received repeat I4F-PCC dosing. The median ICU length of stay (LOS) was 3 days (IQR 2-7 days), median hospital LOS was 6 days (IQR 3-12 days), and overall mortality rate was 28.8%. For institutions rounding doses to the nearest vial size, the first post-I4F-PCC dose INR was statistically but not clinically significantly lower than for institutions without vial size dose rounding, with comparable degrees of INR reduction from baseline. No differences were observed between dose rounding cohorts in adverse effects, ICU or hospital LOS, modified Rankin score at discharge, or mortality rates. CONCLUSIONS: Most patients received single doses of I4F-PCC, with adjunctive reversal agents and rounding doses to vial size. The time difference from baseline INR to factor product administration is a potential opportunity for process improvement in the management of warfarin-related ICH.

A selective small-molecule inhibitor of macrophage migration inhibitory factor-2 (MIF-2), a MIF cytokine superfamily member, inhibits MIF-2 biological activity.

Cytokine macrophage migration inhibitory factor-2 (MIF-2 or D-dopachrome tautomerase) is a recently characterized second member of the MIF cytokine superfamily in mammalian genomes. MIF-2 shares pro-inflammatory and tumorigenic properties with the clinical target MIF (MIF-1), but the precise contribution of MIF-2 to immune physiology or pathology is unclear. Like MIF-1, MIF-2 has intrinsic keto-enol tautomerase activity and mediates biological functions by engaging the cognate, common MIF family receptor CD74. Evidence that the catalytic site of MIF family cytokines has a structural role in receptor binding has prompted exploration of tautomerase inhibitors as potential biological antagonists and therapeutic agents, although few catalytic inhibitors inhibit receptor activation. Here we describe the discovery and biochemical characterization of a selective small-molecule inhibitor of MIF-2. An in silico screen of 1.6 million compounds targeting the MIF-2 tautomerase site yielded several hits for potential catalytic inhibitors of MIF-2 and identified 4-(3-carboxyphenyl)-2,5-pyridinedicarboxylic acid (4-CPPC) as the most functionally potent compound. We found that 4-CPPC has an enzymatic IC50 of 27 µm and 17-fold selectivity for MIF-2 versus MIF-1. An in vitro binding assay for MIF-1/MIF-2 to the CD74 ectodomain (sCD74) indicated that 4-CPPC inhibits MIF-2-CD74 binding in a dose-dependent manner (0.01-10 µm) without influencing MIF-1-CD74 binding. Notably, 4-CPPC inhibited MIF-2-mediated activation of CD74 and reduced CD74-dependent signal transduction. These results open opportunities for development of more potent and pharmacologically auspicious MIF-2 inhibitors to investigate the distinct functions of this MIF family member in vivo.

In Vivo Morphological Study of Common Canalicular Orifice and Its Impact on Lacrimal Probing.

PURPOSE: To study the in vivo morphology of common canalicular/lacrimal sac mucosal folds (CLS-MFs) and their relationship with probing findings. METHODS: Consecutive cases undergoing endoscopic dacryocystorhinostomy had endoscopic examination of the internal canalicular orifice (ICO). Details of CLS-MFs folds, probing findings, and outcomes of dacryocystorhinostomy were analyzed. RESULTS: Thirty-six lacrimal systems of 34 patients (mean age, 58 years; 7 males, 27 females) were examined. All 36 lacrimal systems had a single common canalicular orifice entering the lacrimal sac (100%). Overall, 61.1% (22/36) had visible CLS-MFs, out of which only 13.6% (3/22) were overhanging the ICO requiring manipulation of the probe to enter the lacrimal sac. The orientation of folds was superior 180° in 2, posterosuperior in 2, posterior in 6, inferior 180° in 6, and inferior 270° (excluding 10-2'o clock quadrant) in 6 systems. Two cases preoperatively labeled as having common canalicular obstruction, based on lacrimal syringing, had CLS-MFs impacting against the ICO without any anatomical obstruction. One of 5 cases with lacrimal sac mucocele had CLS-MFs located along the posterosuperior edge extending for 270°, which resulted in a soft stop on preoperative lacrimal syringing findings. Only 1 case had a true membrane (2.7%) overlying the ICO, which required excision. No differences in outcomes of dacryocystorhinostomy were observed between cases with CLS-MFs versus without any folds. CONCLUSION: CLS-MFs display a wide variation in terms of morphological location and extent along the ICO. They might be responsible for the false soft stop observed in some cases on preoperative syringing and do not require excision.

In Vivo Morphology of Nasolacrimal Duct Opening into the Inferior Meatus.

PURPOSE: To study the in vivo morphology of nasolacrimal duct (NLD) openings into the inferior meatus. METHODS: Patients undergoing endoscopic dacryocystorhinostomy and lacrimal intubation had endoscopic real-time examination of the NLD opening. Morphology of NLD openings (size, shape, mucosal folds), and their location from the axilla of the inferior turbinate were assessed. RESULTS: Forty-three lacrimal systems of 39 adult patients (11 males, 28 females) with a mean age of 61 years were studied. Thirty-five patients had unilateral involvement, and 74% had anatomical NLD obstruction. Of 43 lacrimal systems, 41 had a visible NLD opening. The majority was sulci shaped (63%, 26/41) followed by fissure type (34%), and 2% had wide-open round morphology. The majority of the openings (93%) were oriented vertically, and 67% (14/21) of the sulci shaped openings continued into gutter like channels along the lateral nasal wall. Mucosal folds were present in 7% (3/41) of the openings along the edges. The mean distance between the opening and the axilla of the inferior turbinate was 3.7± 2.1 mm (median, 3.6; range, 0-7.2). CONCLUSION: Sulci shaped NLD openings were the most common morphology, and mucosal folds were less commonly observed compared with cadaveric studies.

Impact of birth cohort screening for hepatitis C.

Hepatitis C (HCV) is a leading cause of liver-related complications, and the burden of liver disease is expected to increase. Given the over-representation of HCV-related liver disease in persons born between 1945 and 1965, and the failure of risk-based screening to identify many infected persons, birth cohort screening has been advocated and endorsed by both the Centers for Disease Control and United States Preventive Services Task Force, regardless of the presence of risk factors. Birth cohort testing is more cost-effective than risk-based screening especially when those with more advanced disease are given priority for treatment. Several barriers exist at the patient and provider level that need to be overcome to fully realize the potential benefit of birth cohort screening in reducing HCV-related morbidity and mortality.

Event-horizon-scale structure in the supermassive black hole candidate at the Galactic Centre.

The cores of most galaxies are thought to harbour supermassive black holes, which power galactic nuclei by converting the gravitational energy of accreting matter into radiation. Sagittarius A* (Sgr A*), the compact source of radio, infrared and X-ray emission at the centre of the Milky Way, is the closest example of this phenomenon, with an estimated black hole mass that is 4,000,000 times that of the Sun. A long-standing astronomical goal is to resolve structures in the innermost accretion flow surrounding Sgr A*, where strong gravitational fields will distort the appearance of radiation emitted near the black hole. Radio observations at wavelengths of 3.5 mm and 7 mm have detected intrinsic structure in Sgr A*, but the spatial resolution of observations at these wavelengths is limited by interstellar scattering. Here we report observations at a wavelength of 1.3 mm that set a size of 37(+16)(-10) microarcseconds on the intrinsic diameter of Sgr A*. This is less than the expected apparent size of the event horizon of the presumed black hole, suggesting that the bulk of Sgr A* emission may not be centred on the black hole, but arises in the surrounding accretion flow.

Economic model of a birth cohort screening program for hepatitis C virus.

UNLABELLED: Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus $53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus $39.8 billion); birth-cohort screening produces an incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus risk-based screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs. CONCLUSION: Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness-to-pay thresholds.

Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation.

Liver transplantation is the optimal treatment for patients with hepatocellular carcinoma (HCC) and cirrhosis. This study was conducted to determine the impact of pre-transplant locoregional therapy (LRT) on HCC and our institution's experience with expansion to United Network of Organ Sharing Region 4 T3 (R4T3) criteria. Two hundred and twenty-five patients with HCC (176 meeting Milan and 49 meeting R4T3 criteria) underwent liver transplantation from 2002 to 2008. Compared with the Milan criteria, HCCs in R4T3 criteria displayed less favorable biological features such as higher median alpha-fetoprotein level (21.9 vs. 8.5 ng/mL, p = 0.01), larger tumor size, larger tumor number, and higher incidence of microvascular invasion (22% vs. 5%, p = 0.002). As a result, patients meeting Milan criteria had better five-yr survival (79% vs. 69%, p = 0.03) and a trend toward lower HCC recurrence rates (5% vs. 13%, p = 0.05). Pre-transplant LRT did not affect post-transplant outcomes in patients meeting Milan criteria but did result in lower three-yr HCC recurrence (7% vs. 75%, p < 0.001) and better three-yr survival (p = 0.02) in patients meeting R4T3 criteria. Tumor biology and pre-transplant LRT are important factors that determine the post-transplant outcomes in patients with HCC who meet R4T3 criteria.

Long-term outcomes of stereotactic body radiation therapy in the treatment of hepatocellular cancer as a bridge to transplantation.

Hepatocellular carcinoma (HCC) is potentially curable with hepatic resection or transplantation. Few patients are eligible for resection, and many face a long wait for donor organ availability for liver transplantation. Here we report the safety and efficacy of stereotactic body radiation therapy (SBRT), the explant pathology findings and survival of patients treated with SBRT as a bridge to transplantation for HCC. From April 2005 to August 2010, 10 patients with 11 HCCs were treated with SBRT as a bridge to transplantation. All patients were evaluated by a liver transplant surgeon before radiosurgery. SBRT was delivered with the CyberKnife robotic radiosurgery system. After SBRT, all patients underwent orthotopic liver transplantation. The tumor response was determined by explant pathology. The median follow-up was 62 months from the time of SBRT. The mean time on the liver transplant wait list was 163 days. The median tumor size was 3.4 cm (range = 2.5-5.5 cm). The median SBRT dose was 51 Gy (range = 33-54 Gy) in 3 fractions. The median time from SBRT to liver transplantation was 113 days (range = 8-794 days). At 5 years, the overall survival rate and the disease-free survival rate were both 100%. Overall, 4 of the 10 patients (40%) experienced acute toxicity. Most toxicities were grade 1, and they included nausea, fatigue, and abdominal discomfort. One patient had grade 2 nausea/vomiting. Explant pathology revealed no viable tumor in 3 of the 11 tumors for a complete response rate of 27%. The remaining 8 tumors decreased or remained stable in size. In conclusion, with a median follow-up over 5 years, we have found that SBRT as a bridge to liver transplantation for HCC is feasible and well tolerated. SBRT for HCC may enable patients to remain on the list for frequently curative transplantation during the wait for organ availability.

Utilization of hepatitis C antibody-positive livers: genotype dominance is virally determined.

Because of the unrelenting donor shortage, utilization of all potential liver donors is essential. However, when utilizing marginal donors it is critical to precisely characterize the risks, inform recipients of those risks, and allocate these higher risk organs to appropriate candidates. Towards this goal, we need to determine the safety and potential consequences, if any, of utilizing hepatitis C (HCV) antibody-positive donors in HCV infected recipients. To further characterize HCV antibody-positive donors, we analyzed prospectively collected serum samples from HCV antibody-positive donors transplanted into HCV RNA-positive recipients from 5/1993 to 10/2008 for HCV viral load (Roche Cobas AmpliPrep/Cobas Taqman HCV Assay) and genotype (Siemens Versant 2.0 LiPA HCV 5' UTR/Core Assay). Seventeen of 32 (53%) HCV antibody-positive donors were RNA negative. Fifteen patients received an HCV RNA-positive donor and nine donor-recipient pairs had different genotypes or subtypes for analysis. When genotype 1 competed with a non-1 genotype, it was found in 5/6 recipients. In 2/3 cases of mismatched genotype 1 subtypes, genotype 1a dominated. Kaplan-Meier analysis of patient and graft survival and fibrosis progression did not reveal differences between patients who received an HCV antibody-positive donor that was viremic or aviremic. In conclusion, approximately half of HCV antibody-positive donors were aviremic. Viral dominance in viremic donor-recipient pairs seems virally determined.

Asymmetric synthesis and evaluation of a hydroxyphenylamide voltage-gated sodium channel blocker in human prostate cancer xenografts.

Voltage-gated sodium channels are known to be expressed in neurons and other excitable cells. Recently, voltage-gated sodium channels have been found to be expressed in human prostate cancer cells. α-Hydroxy-α-phenylamides are a new class of small molecules that have demonstrated potent inhibition of voltage-gated sodium channels. The hydroxyamide motif, an isostere of a hydantoin ring, provides an active scaffold from which several potent racemic sodium channel blockers have been derived. With little known about chiral preferences, the development of chiral syntheses to obtain each pure enantiomer for evaluation as sodium channel blockers is important. Using Seebach and Frater's chiral template, cyclocondensation of (R)-3-chloromandelic acid with pivaldehyde furnished both the cis- and trans-2,5-disubsituted dioxolanones. Using this chiral template, we synthesized both enantiomers of 2-(3-chlorophenyl)-2-hydroxynonanamide, and evaluated their ability to functionally inhibit hNa(v) isoforms, human prostate cancer cells and xenograft. Enantiomers of lead demonstrated significant ability to reduce prostate cancer in vivo.

Evaluation of thermotherapy for the treatment of cutaneous leishmaniasis in Kabul, Afghanistan: a randomized controlled trial.

Anthroponotic cutaneous leishmaniasis (CL) is a common cause of ulcerative lesions and disfiguring scarring among children in Afghanistan. Most lesions occur on the face and are commonly caused by the trypanosome protozoan parasite Leishmania tropica, transmitted by the bite of an infected sandfly (Phlebotomus sergenti). This study compared the effectiveness of a single localized treatment with thermotherapy to 5 days of intralesional administration of Glucantime for the treatment of CL. Three hundred and eighty-two patients with CL were randomly assigned to the two treatment groups and followed for 6 months. The cure rate for the thermotherapy group was 82.5%, compared to 74% in the Glucantime group. The authors concluded that a single localized treatment with thermotherapy was more effective than 5 days of intralesional administration of Glucantime. Additionally, thermotherapy was more cost-effective, with fewer side effects, of shorter duration, and with better patient compliance than intralesional Glucantime.

Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression.

BACKGROUND & AIMS: The prevalence of chronic hepatitis C (CH-C) remains high and the complications of infection are common. Our goal was to project the future prevalence of CH-C and its complications. METHODS: We developed a multicohort natural history model to overcome limitations of previous models for predicting disease outcomes and benefits of therapy. RESULTS: Prevalence of CH-C peaked in 2001 at 3.6 million. Fibrosis progression was inversely related to age at infection, so cirrhosis and its complications were most common after the age of 60 years, regardless of when infection occurred. The proportion of CH-C with cirrhosis is projected to reach 25% in 2010 and 45% in 2030, although the total number with cirrhosis will peak at 1.0 million (30.5% higher than the current level) in 2020 and then decline. Hepatic decompensation and liver cancer will continue to increase for another 10 to 13 years. Treatment of all infected patients in 2010 could reduce risk of cirrhosis, decompensation, cancer, and liver-related deaths by 16%, 42%, 31%, and 36% by 2020, given current response rates to antiviral therapy. CONCLUSIONS: Prevalence of hepatitis C cirrhosis and its complications will continue to increase through the next decade and will mostly affect those older than 60 years of age. Current treatment patterns will have little effect on these complications, but wider application of antiviral treatment and better responses with new agents could significantly reduce the impact of this disease in coming years.

Patients with NASH and cryptogenic cirrhosis are less likely than those with hepatitis C to receive liver transplants.

BACKGROUND & AIMS: Many patients with cryptogenic cirrhosis (CC) have other conditions associated with nonalcoholic steatohepatitis (NASH) that put them at risk for complications that preclude orthotopic liver transplantation (OLT). METHODS: We followed all patients with NASH and CC who were evaluated for OLT (n = 218) at Baylor Simmons Transplant Institute between March 2002 and May 2008. Data were compared with those from patients evaluated for OLT because of hepatitis C virus (HCV)-associated cirrhosis (n = 646). RESULTS: Patients with NASH and CC were older, more likely to be female, had a higher body mass index, and a greater prevalence of diabetes and hypertension, compared with patients with HCV-associated cirrhosis, but the 2 groups had similar model for end-stage liver disease (MELD) scores. NASH and CC in patients with MELD scores ≤15 were less likely to progress; these patients were less likely to receive OLT and more likely to die or be taken off the wait list because they were too sick, compared with patients with HCV-associated cirrhosis. The median progression rate among patients with NASH and CC was 1.3 MELD points per year versus 3.2 MELD points per year for the HCV group (P = .003). Among patients with MELD scores >15, there were no differences among groups in percentage that received transplants or rate of MELD score progression. Hepatocellular carcinoma occurred in 2.7% of patients with NASH and CC per year, compared with 4.7% per year among those with HCV-associated cirrhosis. CONCLUSIONS: Patients with NASH and CC and low MELD scores have slower disease progression than patients with HCV-associated cirrhosis and are less likely to receive OLT.

A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C.

This randomized, prospective, multicenter trial compared the safety and efficacy of steroid-free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA-positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid-free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ≥ 3 and/or a fibrosis stage ≥ 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS.

Clinical vignettes in geriatric depression.

The diagnosis of depression in older patients is often complicated by comorbid conditions, such as cerebrovascular disease or dementia. Tools specific for this age group, such as the Geriatric Depression Scale or the Cornell Scale for Depression in Dementia, may assist in making the diagnosis. Treatment decisions should consider risks associated with medications, such as serotonin syndrome, hyponatremia, falls, fractures, and gastrointestinal bleeding. Older white men with depression are at high risk of suicide. Depression is common after stroke or myocardial infarction, and response to antidepressant treatment has been linked to vascular outcomes. Depression care management is an important adjunct to the use of antidepressant medications. Structured psychotherapy and exercise programs are useful treatments for select patients.

Lessons learned from casualty statistics in health care system development: Afghanistan 2008-2009.

A retrospective study of Afghanistan National Army casualty rates for a 1-year period was completed to assist in health care system assessment and further development during a period of rapid force expansion. Battle and disease nonbattle injuries by Corps area were determined from data on soldier visits from all military health care facilities. The number of fielded forces in each Corps was used to calculate the populations at risk. Total manpower losses from all casualties were tabulated. The 15,336 casualties (175 per thousand fielded soldiers) resulted in the loss of 146,986 duty days (average 9.5 days per casualty). Battle casualties were 739 (8.4 per 1,000) and nonbattle casualties were 14,597(166 per 1,000) with 72% secondary to infectious diseases. Casualty rates from both battle and disease nonbattle injuries were high, but casualty rates were particularly high from infectious diseases. Rapid force expansion in developing countries requires early consideration for resourcing and implementation of preventive medicine programs.