Rapid Therapeutic Response Research Articles

Augmentation with carnicetine for late depression

Comparative evaluation of the efficacy and safety of antidepressant monotherapy and complex antidepressant therapy in combination with carnicetine in the treatment of depression in elderly patients in a psychiatric hospital. Two groups of hospitalized patients, aged from 60 to 79 years, with mild or moderate depression (according to ICD-10), comparable in basic demographic and clinical characteristics, received mono- or complex (in combination with carnicetine) antidepressant therapy for 8 weeks. Treatment efficacy was assessed with HAM-D, HARS, CGI-S and CGI-I; the level of cognitive activity was assessed with MMSE, the 10-word memory test and clock drawing test. It has been established that the use of complex antidepressants therapy with the inclusion of carnicetine allows to achieve a more rapid and pronounced therapeutic response compared to antidepressant monotherapy. This is confirmed by the earlier (by the 4th week) and significant reduction of depressive and anxiety symptoms (p<0.01), a greater number of responders and better quality of depressive outcomes to the end of treatment and a more rapid improvement in cognitive functioning. The results allow us to recommend the inclusion of carnicetine for the augmentation of antidepressant therapy in elderly patients of the psychiatric hospital to achieve a more rapid and complete therapeutic response and reduce the duration of hospitalization.

Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.

Measuring the functional status of tumor vasculature, including blood flow fluctuations and changes in oxygenation, is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths, OT can interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumor hypoxia quantified ex vivo Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods.Significance: Imaging biomarkers derived from optoacoustic tomography can be used as surrogate measures of tumor perfusion and hypoxia, potentially yielding rapid, multiparametric, and noninvasive cancer staging and therapeutic response monitoring in the clinic.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg Cancer Res; 78(20); 5980-91. ©2018 AACR.

D-Serine is a potential biomarker for clinical response in treatment of post-traumatic stress disorder using (R,S)-ketamine infusion and TIMBER psychotherapy: A pilot study

Post-traumatic stress disorder (PTSD) is a chronic and debilitating condition that is often refractory to standard frontline antidepressant therapy. A promising new approach to PTSD therapy is administration of a single sub-anesthetic dose of (R,S)-ketamine (Ket). The treatment produces rapid and significant therapeutic response, which lasts for only 4–7 days. In one of our studies, the mean duration of response was increased to 33 days when Ket administration was combined with a mindfulness-based cognitive therapy, Trauma Interventions using Mindfulness Based Extinction and Reconsolidation (TIMBER). We now report the results from a 20-patient study, which examined the duration of sustained response with combined TIMBER-Ket therapy, TIMBER-K arm, relative to the response observed in a placebo-controlled arm, TIMBER-P. A significant difference in the duration of response was observed between TIMBER-K and TIMBER-P arms: 34.44 ± 19.12 days and 16.50 ± 11.39 days, respectively (p = 0.022). Previous studies identified a negative correlation between antidepressant response to Ket and basal plasma concentrations of d-serine (DSR). In this study, the basal DSR levels positively correlated with the pre-treatment severity of PTSD symptoms (Pearson's r = 0.42, p = 0.07) and patients with basal DSR level ≥ 3.5 μM displayed not only higher PTSD severity but also shorter duration of response. The data indicate that basal DSR levels may serve as a biomarker of the severity of PTSD symptoms and as a predictor of clinical response. This article is part of a Special Issue entitled: d-Amino acids: biology in the mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.

Potential Bedside Utility of the Clock-Drawing Test in Evaluating Rapid Therapeutic Response in the Natural Course of Schizophrenia: A Preliminary Study

The Clock-Drawing Test (CDT) is a brief, relatively time-efficient, easy to administer at bedside, and well-proven cognitive screening test that assesses a broad range of cognitive abilities in stroke, delirium, and dementia. However, challenges of comprehensive therapeutic outcome evaluations in schizophrenia can also be potentially overcome using CDT. The authors aimed to measure the therapeutic outcome using CDT in 101 schizophrenia patients, irrespective of their diagnostic subtypes. A repeated measures analysis of variance found that improvements on CDT and the Positive and Negative Syndrome Scale were closely correlated, reflecting critical information about therapeutic response measures in schizophrenia.

Ratios of biochemical markers in peritoneal fluid to those in venous blood for the diagnosis of ruptured tubal pregnancy: A prospective study

ObjectivesEctopic pregnancies are among the leading causes of maternal morbidity and mortality in both developed and emerging nations, but tests for early, accurate, and convenient detection are lacking.Study DesignBetween January 2013 and February 2015, 504 women with tubal pregnancy were prospectively recruited, and their clinical characteristics were recorded. Samples of peritoneal fluid were collected by culdocentesis, and venous blood was drawn from the antecubital vein. In samples from each source, levels of the following biochemical markers were measured: cancer antigen 125 (CA125), human chorionic gonadotropin (hCG), progesterone, vascular endothelial growth factor, and creatine kinase. ResultsThe ratios of biochemical markers in the peritoneal fluid and in the blood (Rp/v) were calculated. The median of Rp/v-CA125 and Rp/v-hCG were significantly lower in the ruptured ectopic pregnancy group than in the unruptured group. The optimal cutoff value to detect ectopic pregnancy rupture was 401.5U/mL as the upper limit for peritoneal CA125, with a sensitivity of 93.5% and specificity of 74.2%. The optimal cutoff value was 18.7 as the upper limit in the peritoneal fluid/blood ratio (Rp/v) of CA125, with a sensitivity of 77.5% and specificity of 68.4%. ConclusionsIn countries with poor access to laparoscopy, culdocentesis is useful. In this study, culdocentesis provided additional information for management of abdominal pain when laparoscopy is not available. The authors propose Rp/v cutoff values that can be used conveniently and quickly to diagnose ruptured ectopic pregnancies and bleeding, enabling rapid and appropriate therapeutic responses.

Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants.

Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although mechanisms by which ketamine/esketamine may produce antidepressant effects have been hypothesized on the basis of preclinical data, the neurobiological correlates of the rapid therapeutic response observed in patients receiving treatment have not been established. Here we use a pharmacometabolomics approach to map global metabolic effects of these compounds in treatment-refractory MDD patients upon 2 h from infusion with ketamine (n=33) or its S-enantiomer, esketamine (n=20). The effects of esketamine on metabolism were retested in the same subjects following a second exposure administered 4 days later. Two complementary metabolomics platforms were used to provide broad biochemical coverage. In addition, we investigated whether changes in particular metabolites correlated with treatment outcome. Both drugs altered metabolites related to tryptophan metabolism (for example, indole-3-acetate and methionine) and/or the urea cycle (for example, citrulline, arginine and ornithine) at 2 h post infusion (q<0.25). In addition, we observed changes in glutamate and circulating phospholipids that were significantly associated with decreases in depression severity. These data provide new insights into the mechanism underlying the rapid antidepressant effects of ketamine and esketamine, and constitute some of the first detailed metabolomics mapping for these promising therapies.

Artesunate–mefloquine versus chloroquine for treatment of uncomplicated Plasmodium knowlesi malaria in Malaysia (ACT KNOW): an open-label, randomised controlled trial

The zoonotic parasite Plasmodium knowlesi has become the most common cause of human malaria in Malaysia and is present throughout much of southeast Asia. No randomised controlled trials have been done to identify the optimum treatment for this emerging infection. We aimed to compare artesunate-mefloquine with chloroquine to define the optimum treatment for uncomplicated P knowlesi malaria in adults and children. We did this open-label, randomised controlled trial at three district hospitals in Sabah, Malaysia. Patients aged 1 year or older with uncomplicated P knowlesi malaria were randomly assigned, via computer-generated block randomisation (block sizes of 20), to receive oral artesunate-mefloquine (target dose 12 mg/kg artesunate and 25 mg/kg mefloquine) or chloroquine (target dose 25 mg/kg). Research nursing staff were aware of group allocation, but allocation was concealed from the microscopists responsible for determination of the primary endpoint, and study participants were not aware of drug allocation. The primary endpoint was parasite clearance at 24 h. Analysis was by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01708876. Between Oct 16, 2012, and Dec 13, 2014, we randomly assigned 252 patients to receive either artesunate-mefloquine (n=127) or chloroquine (n=125); 226 (90%) patients comprised the modified intention-to-treat population. 24 h after treatment, we recorded parasite clearance in 97 (84% [95% CI 76-91]) of 115 patients in the artesunate-mefloquine group versus 61 (55% [45-64]) of 111 patients in the chloroquine group (difference in proportion 29% [95% CI 18·0-40·8]; p<0·0001). Parasite clearance was faster in patients given artesunate-mefloquine than in those given chloroquine (18·0 h [range 6·0-48·0] vs 24·0 h [6·0-60·0]; p<0·0001), with faster clearance of ring stages in the artesunate-mefloquine group (mean time to 50% clearance of baseline parasites 8·6 h [95% CI 7·9-9·4] vs 13·8 h [12·1-15·4]; p<0·0001). Risk of anaemia within 28 days was lower in patients in the artesunate-mefloquine group (71 [62%; 95% CI 52·2-70·6]) than in those in the chloroquine group (83 [75%; 65·6-82·5]; p=0·035). Gametocytaemia as detected by PCR for pks25 was present in 44 (86%) of 51 patients in the artesunate-mefloquine group and 41 (84%) of 49 patients in the chloroquine group at baseline, and in three (6%) of 49 patients and two (4%) of 48 patients, respectively, at day 7. Fever clearance was faster in the artesunate-mefloquine group (mean 11·5 h [95% CI 8·3-14·6]) than in the chloroquine group (14·8 h [11·7-17·8]; p=0·034). Bed occupancy was 2426 days per 1000 patients in the artesunate-mefloquine group versus 2828 days per 1000 patients in the chloroquine group (incidence rate ratio 0·858 [95% CI 0·812-0·906]; p<0·0001). One (<1%) patient in the artesunate-mefloquine group had a serious neuropsychiatric event regarded as probably related to study drug. Artesunate-mefloquine is highly efficacious for treatment of uncomplicated P knowlesi malaria. The rapid therapeutic response of the drug offers significant advantages compared with chloroquine monotherapy and supports a unified treatment policy for artemisinin-based combination therapy for all Plasmodium species in co-endemic areas. Malaysian Ministry of Health, Australian National Health and Medical Research Council, and Asia Pacific Malaria Elimination Network.

Тразодон у лікуванні депресії після інсульту

Стаття присвячена проблемі депресії у пацієнтів, які перенесли інсульт. Доведена її актуальність, розглянуто поширеність у даної категорії хворих. Докладно висвітлено патогенез. Щодо лікування постінсультної депресії підкреслюється, що медикаментозна терапія повинна розглядатися як складова частина процесу реабілітації в усіх хворих, які перенесли інсульт. Відповідно до рекомендацій FDA, одним із найбільш оптимальних препаратів для лікування пацієнтів, які страждають від постінсультної депресії, є тразодон. Тразодон характеризується помірним інгібуванням зворотного захвату серотоніну і сильною блокадою серотонінових рецепторів. Крім антидепресивного впливу, він справляє дуже добрий анксіолітичний ефект, що можна порівняти з таким у хлордіазепоксиду та діазепаму. Беручи до уваги седативні властивості та сприятливий вплив на структуру сну, застосовується також як снодійне переважно тоді, коли прийом снодійних препаратів бензодіазепінового ряду пов’язаний з підвищеним ризиком. Клінічні дослідження попередніх років показують, що завдяки поєднаному впливу на різні групи рецепторів тразодон має значно менш виражені побічні ефекти та швидку терапевтичну відповідь.

Neurocirculatory Manifestations of Thiamine Deficiency

The diagnosis of thiamine deficiency is essentially made on clinical grounds and may present with neurological deficit such as peripheral neuropathy and Wernicke’s encephalopathy, or with high output heart failure (wet beriberi). This study was done to determine the frequency with which both the neurological and cardiovascular manifestations coexist in states of thiamine deficiency. The hospital records of 186 patients admitted on 200 occasions with a diagnosis of thiamine deficiency due to beriberi or Wernickes encephalopathy were reviewed during the 7-year period (1994-2000). Cases were only included in the analysis if mental changes and neurological deficit (opthalmoplegia, ataxia, nystagmus) resolved rapidly after treatment with thiamine. Similar to the neurological recovery with thiamine, a rapid response in the cardiovascular state and in the metabolic acidosis to treatment with parenteral thiamine was taken as confirmatory evidence of thiamine deficiency. In all but 11 patients, complete recovery ensued within 1-3 days of treatment with parenteral thiamine. The 175 patients who responded dramatically to thiamine (67 Wernicke’s encephalopathy and 108 cardiac beriberi) form the subject of this review. In total, 43/175 (25%) patients exhibited combined neurologic and circulatory manifestations of thiamine deficiency. Eighteen patients presented with overt coexisting neurocardiac manifestations, twelve of whom had acute pernicious beriberi with circulatory shock, metabolic acidosis and accompanying neurological deficit. There was one death due to circulatory shock and metabolic acidosis in patient who arrived in extremis with an unrecordable blood pressure at the emergency room. Cardiovascular/circulatory manifestations in patients presenting with acute neurological deficit are not infrequent and should raise suspicion of thiamine deficiency. Likewise patients with advanced thiamine deficiency states presenting with shock and metabolic acidosis not infrequently have coexistent signs of WE. Empiric therapy with thiamine in advanced stages of thiamine deficiency is life-saving and a rapid therapeutic response is confirmatory of the diagnosis.

Zinc-responsive acral hyperkeratotic dermatosis-A novel entity or a subset of some well-known dermatosis?

Background:We are reporting a series of interesting cases, which presented to us with psoriasiform lesions distributed over the acral regions of the body. The cases are unusual because they were resistant to conventional treatment modalities like topical corticosteroids, tacrolimus and oral methotrexate but showed significant improvement on oral zinc therapy.Materials and Methods:Ten patients with characteristic clinical features of distinctive hyperkeratotic plaque in the acral areas, who were resistant to treatment by different modalities including potent topical steroids and oral methotrexate, were included for detailed investigations. A proper history was taken and relevant laboratory investigations were done which included blood count, urine, liver function, renal function, hepatitis-C virus serology and serum zinc levels. Patients were followed up every 2 weeks. Histopathological examinations of the lesional tissue were done at baseline and after 6 weeks of therapy. Patients were given oral zinc daily and no other treatment during the 6 weeks course.Results:All our patients were non-reactive to hepatitis-C. Of the ten patients only one patient (10%) showed low titer of serum zinc, another (10%) showed higher zinc level, while the rest of the patients had normal zinc level. Five of our patients had chronic renal failure, one had Grave's disease and the remaining had no associated systemic illness. Histopathology mostly showed hyperkeratosis, acanthosis, prominent granular layer, spongiosis and dermal infiltrate. After 6 weeks of follow up, all patients showed rapid and remarkable therapeutic response with zinc.Conclusions:We here report a series of patients, discernible because of their uniform clinical presentation of acral hypekeratotic plaques and in showing a noticeable response to zinc. Clinical, histopathological and laboratory investigations were done to rule out diseases of similar morphology including psoriasis, acral necrolytic erythema and lichen simplex chronicus. Authors understand that further studies with greater number cases and more detailed investigations are required to establish exact etio-pathogenesis and nomenclature of this distinct subset of patients.

Drops Supplementation for Treating Vitamin D Deficiency in Healthy Children and Adolescents: The Important Role of Sun Exposure

Background: High prevalence of Vit D deficiency had been worldwide reported and supplementation was recommended in deficient cases with rapid therapeutic response. As there is no clear evidence to what really is required during childhood in order to prevent adult diseases, this study aimed to evaluate the effectiveness of supplementation therapy in healthy children with vit D deficiency. Methods: Thirty six children, mean age 10.9+3.4 years old, with Vit D deficiency were included in the study and were randomly divided in two groups: Those who received supplementation therapy with 2000 IU Vit D3 drops daily for three months and those who had no intervention. Socioeconomic status, sun protection and diet habits, outdoors physical activity and fracture history were evaluated through a questionnaire and blood samples before and after intervention were collected to assess 25(OH)Vit D levels and bone mineral status. Results: There was no significant difference between the two groups in relation to socioeconomic and family characteristic, outdoors physical activity and dietary intake. Sunscreen use was limited during summer vacation in 85% of the cases but the amount of use was significantly negatively correlated to baseline levels of Vit D during last year. The 25(OH)Vit D levels at baseline were 14.72+3.63 ng/ml (6.7 - 19.7 ng/ml) whereas a significant increase 25.21+7.08 ng/ml (8-42.2 ng/ml) was observed on re-evaluation (p=0.0001). No difference was found between treated children and non-treated (p=0.13). Skin type and sunscreen habits were not related to therapeutic response rate in both groups. Conclusion: This randomized clinical trial revealed a significant improvement in Vit D levels both in treated and non treated groups but no significant difference was established between the groups. The supplementation of vit D in healthy children and adolescents with Vit D deficiency could not be suggested. Sun protection may interfere with Vit D levels. Re-evaluation and re discussion of sun health benefits on Vit D synthesis and national sun protection strategies may be needed.

Rapid antidepressant effects: moving right along

Available treatments for depression have significant limitations, including low response rates and substantial lag times for response. Reports of rapid antidepressant effects of a number of compounds, including the glutamate N-methyl-D-aspartate receptor antagonist ketamine, have spurred renewed translational neuroscience efforts aimed at elucidating the molecular and cellular mechanisms of action that result in rapid therapeutic response. This perspective provides an overview of recent advances utilizing compounds with rapid-acting antidepressant effects, discusses potential mechanism of action and provides a framework for future research directions aimed at developing safe, efficacious antidepressants that achieve satisfactory remission not only by working rapidly but also by providing a sustained response.

1371 – Significant polypharmacy in patients with psychiatric disorders

Polypharmacy involving prescribed medications in the psychiatric population is increasing. The main psychiatric reason is to gain rapid therapeutic response as well as to bolster medication effectiveness in treating patients with refractory psychotic symptoms, mood symptoms, or behavioral problems. This may also increase the need for additional medications to treat side-effects. Further, these patients have significant co-morbid conditions, requiring additional non-psychiatric medications. To examine polypharmacy amongst psychiatric patients during their visit to an internist's office. To confirm the presence of significant polypharmacy in patients with psychiatric diseases. All patients seen in our office from residential boarding homes and under care of psychiatrists were included in the study. A list of all medications (antipsychotic and non-psychiatric) were obtained from the boarding home, office charts and pharmacy and tabulations done. Polypharmacy was defined as 5-9 medications and excessive polypharmacy more than 10 medications. Of the total of 146 patients (92 males, 54 females, aged 24-82 years), 4 (3%) were on one, 6 (4%) on two, 3 (2%) on three, 12 (8%) on four, 9 (6%) one five, 11 (8%) on six,16 (11%) on seven, 14 (10%)on eight, 22 (15%) on nine, 8 (5%) on ten, 41 (28%) on 11 or more medications. Polypharmacy and excessive polypharmacy is common in psychiatric patients. Monotherapy was extremely rare, with only 4 patients (3%) being on only one drug. Our data suggests that polypharmacy in a residential psychiatric population is more common and more severe than previously reported.

Lichen planus with palmoplantar involvement: rapid therapeutic response to acitretin

ejd.2011.1453 Auteur(s) : Yue-Ping Zeng, Qiu-Ning Sun sunqnzhy@yahoo.com, Yue-Hua Liu, Kai Fang Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China Lichen planus (LP) is a common inflammatory dermatosis with unknown etiology [1], clinically characterized by purple, polygonal, pruritic papules or plaques affecting the flexor aspects of the wrists, arms, legs, and mucous membranes [1]. Palmoplantar involvement [...]

Antipsychotic Polypharmacy in Schizophrenia

Antipsychotic polypharmacy refers to the co-prescription of more than one antipsychotic drug for an individual patient. Surveys of prescribing in psychiatric services internationally have identified the relatively frequent and consistent use of combined antipsychotics, usually for people with established schizophrenia, with a prevalence of up to 50% in some clinical settings. A common reason for prescribing more than one antipsychotic is to gain a greater or more rapid therapeutic response than has been achieved with antipsychotic monotherapy. However, the evidence on the risks and benefits for such a strategy is equivocal, and not generally considered adequate to warrant a recommendation for its use in routine clinical practice in psychiatry. Combined antipsychotics are a major contributor to high-dose prescribing, associated with an increased adverse effect burden, and of limited value in helping to establish the optimum maintenance regimen for a patient. The relatively widespread use of antipsychotic polypharmacy identified in cross-sectional surveys reflects not only the addition of a second antipsychotic to boost therapeutic response, but also the use of as-required antipsychotic medication (mainly to treat disturbed behaviour), gradual cross-titration while switching from one antipsychotic to another, and augmentation of clozapine with a second antipsychotic where the illness has failed to respond adequately to an optimized trial of clozapine. This review addresses the clinical trial data and other evidence for each of these pharmacological approaches. Also reviewed are examples of systematic, practice-based interventions designed to reduce the prevalence of antipsychotic polypharmacy, most of which have met with only modest success. Guidelines generally agree that if combined antipsychotics are prescribed to treat refractory psychotic illness, this should be after other, evidence-based, pharmacological treatments such as clozapine have been exhausted. Further, their prescription for each patient should be in the context of an individual trial, with monitoring of the clinical response and adverse effects, and appropriate physical health monitoring.

Golimumab: a new anti-TNF-α agent for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease characterized by symmetric arthritis leading to progressive erosion of cartilage and bone. Psoriatic arthritis and ankylosing spondylitis are also inflammatory arthritides that belong to the spondyloarthritides. Disease-modifying anti-rheumatic drugs and biologic therapies including anti-TNF agents are used in their treatment. The TNF antagonists have shown rapid and sustained therapeutic responses. However, a substantial number of patients fail to respond to anti-TNF agents or experience side effects. Golimumab is a human monoclonal antibody to TNF-α requiring less frequent administration compared with current anti-TNF products. Various trials have shown promising results in terms of efficacy and safety in methotrexate-naive and -resistant patients with RA as well as in patients previously treated with other anti-TNF agents. The efficacy of golimumab has also been demonstrated in patients with psoriatic arthritis and ankylosing spondylitis.

Early pandemic influenza (2009 H1N1) in Ho Chi Minh City, Vietnam: a clinical virological and epidemiological analysis.

To date, little is known about the initial spread and response to the 2009 pandemic of novel influenza A ("2009 H1N1") in tropical countries. Here, we analyse the early progression of the epidemic from 26 May 2009 until the establishment of community transmission in the second half of July 2009 in Ho Chi Minh City (HCMC), Vietnam. In addition, we present detailed systematic viral clearance data on 292 isolated and treated patients and the first three cases of selection of resistant virus during treatment in Vietnam. Data sources included all available health reports from the Ministry of Health and relevant health authorities as well as clinical and laboratory data from the first confirmed cases isolated at the Hospital for Tropical Diseases in HCMC. Extensive reverse transcription (RT)-PCR diagnostics on serial samples, viral culture, neuraminidase-inhibition testing, and sequencing were performed on a subset of 2009 H1N1 confirmed cases. Virological (PCR status, shedding) and epidemiological (incidence, isolation, discharge) data were combined to reconstruct the initial outbreak and the establishment of community transmission. From 27 April to 24 July 2009, approximately 760,000 passengers who entered HCMC on international flights were screened at the airport by a body temperature scan and symptom questionnaire. Approximately 0.15% of incoming passengers were intercepted, 200 of whom tested positive for 2009 H1N1 by RT-PCR. An additional 121 out of 169 nontravelers tested positive after self-reporting or contact tracing. These 321 patients spent 79% of their PCR-positive days in isolation; 60% of PCR-positive days were spent treated and in isolation. Influenza-like illness was noted in 61% of patients and no patients experienced pneumonia or severe outcomes. Viral clearance times were similar among patient groups with differing time intervals from illness onset to treatment, with estimated median clearance times between 2.6 and 2.8 d post-treatment for illness-to-treatment intervals of 1-4 d, and 2.0 d (95% confidence interval 1.5-2.5) when treatment was started on the first day of illness. The patients described here represent a cross-section of infected individuals that were identified by temperature screening and symptom questionnaires at the airport, as well as mildly symptomatic to moderately ill patients who self-reported to hospitals. Data are observational and, although they are suggestive, it is not possible to be certain whether the containment efforts delayed community transmission in Vietnam. Viral clearance data assessed by RT-PCR showed a rapid therapeutic response to oseltamivir.

First artemisinin-based antimalarial combination approved for U.S. market

FDA announced April 8 that it approved Novartis AG’s artemether–lumefantrine product, Coartem, for the treatment of acute, uncomplicated malaria infections in adults and children weighing at least 5 kg. The agency said artemether is the first artemisinin approved for use in the United States. Novartis said its antimalarial, containing 20 mg of artemether and 120 mg of lumefantrine per tablet, is to be taken orally for three days. Cure rates with the three-day treatment have exceeded 96%, the company said. Artemisinin compounds, according to the World Health Organization (WHO), produce a rapid therapeutic response and are active against multidrug-resistant Plasmodium falciparum yet well-tolerated by patients. FDA said the most common adverse reactions to artemether–lumefantrine among adults participating in the trials were headache, anorexia, dizziness, physical weakness, and joint or muscle pain. Among children, the most common drug-related adverse reactions were fever, cough, vomiting, anorexia, and headache. Artemether–lumefantrine is one of the combination antimalarial therapies recommended by WHO for countries where falciparum malaria resists the effects of conventional monotherapies, such as chloroquine.

Serum and urinary biomarker signatures for rapid preclinical in vivo assessment of CDK inhibition as a therapeutic approach for PKD

Recent advances in understanding the molecular pathogenesis of polycystic kidney diseases (PKD) are being translated into promising treatments. Currently, a response to therapy in preclinical animal models of PKD can only be evaluated after several weeks of treatment. The availability of biomarkers for rapid efficacy assessment would greatly facilitate the drug development process. Here we applied SELDI-TOF technology to establish serum and urinary biomarker signatures associated with a rapid therapeutic response to cyclin dependent kinase (CDK) inhibitor roscovitine in the jck mouse model of PKD. A set of 74 serum and 56 urinary markers was identified in the group receiving chronic treatment over 5 weeks. This set was further screened for early efficacy biomarkers in acutely (3-5 days) treated animals with mild (26 days of age) and advanced disease (50 days of age). A third group with intermediate disease (33 days of age) received a single injection to monitor rapid changes in protein profiles within 4, 24 or 48 hours after drug administration. Multifactorial comparative analysis of the acutely treated groups identified a set of 20 urinary and 21 serum efficacy biomarkers. This biomarker signature provides a necessary tool for further assessment of CDK inhibitors as therapeutic agents for PKD.

Painful Spinal Cord Compression as a Complication of Extramedullary Hematopoiesis Associated with β-Thalassemia Intermedia

Spinal cord compression due to extramedullary hematopoiesis (EMH) is a rare manifestation of thalassemia. General therapeutic recommendations do not exist. We report a 23 year old male with beta-thalassemia intermedia and back pain resistant to analgetic medication. Multiple extradural mass lesions on MRI of the lumbar spine were identified. Hypertransfusion was initiated with no relief of symptoms. Low dose irradiation with 20 Gy had to be added to achieve adaequate response. With the combination of transfusion therapy and irradiation a rapid and long-lasting relief of symptoms was achieved. 12 month post irradiation the patient is free of pain and neurological symptoms. Clinical awareness of this phenomenon and knowledge of the available treatment option is essential for successful outcome. In treatment refractory symptoms irradiation could successfully contribute to a rapid therapeutic response.