Reduction In Mean Duration Research Articles

Acute or Chronic Exposure to Corticosterone Promotes Wakefulness in Mice.

Elevated glucocorticoid levels triggered by stress potentially contribute to sleep disturbances in stress-induced depression. However, sleep changes in response to elevated corticosterone (CORT), the major glucocorticoid in rodents, remain unclear. Here, we investigated the effects of acute or chronic CORT administration on sleep using electroencephalogram (EEG) and electromyography (EMG) recordings in freely moving mice. Acute CORT exposure rapidly promoted wakefulness, marked by increased episodes and enhanced EEG delta power, while simultaneously suppressing rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, with the latter marked by decreased mean duration and reduced delta power. Prolonged 28-day CORT exposure led to excessive wakefulness and REM sleep, characterized by higher episodes, and decreased NREM sleep, characterized by higher episodes and reduced mean duration. EEG theta activity during REM sleep and delta activity during NREM sleep were attenuated following 28-day CORT exposure. These effects persisted, except for REM sleep amounts, even 7 days after the drug withdrawal. Elevated plasma CORT levels and depressive phenotypes were identified and correlated with observed sleep changes during and after administration. Fos expression significantly increased in the lateral habenula, lateral hypothalamus, and ventral tegmental area following acute or chronic CORT treatment. Our findings demonstrate that CORT exposure enhanced wakefulness, suppressed and fragmented NREM sleep, and altered EEG activity across all stages. This study illuminates sleep alterations during short or extended periods of heightened CORT levels in mice, providing a neural link connecting insomnia and depression.

Anticonvulsant Activity of Lacidipine against Mes- and Ptz-Induced Seizures

Epilepsy is one of the challenging medical conditions affecting neonates, children and elderly. It has affected 1710 to 9780/million populations within India. Although the report of this condition dates to the prehistoric era, drugs for its treatment are not 100% effective and more often lead to toxic effects. Therefore, a potent drug or a drug adjunct is the need-of-the-hour for providing effective control for this neurological condition. The aim of the present study is to evaluate lacidipine, a calcium channel blocker as a protective agent in seizures induced by standard models of epilepsy, namely maximal electroshock seizure model (MES) and Pentylenetetrazole (PTZ). Standard methods for the induction of seizures such as MES and PTZ were performed on male Wistar albino mice. The mice were then treated with vehicle/standard drug (sodium valproate)/ lacidipine. Further, the standard parameters of recovery duration were evaluated. The study revealed that lacidipine at a dose of 3mg/kg body weight significantly reduced the duration of hind limb tonic extension and postictal depression in MES. PTZ-induced seizures showed significantly reduced mean duration of hind limb tonic flexion, hind limb tonic extension, clonus and postictal depression. The findings from the present study suggest that lacidipine has potent anticonvulsant ability in better protection against MES-induced seizures over that of the PTZ-induced one.

Effectiveness of Educational Intervention in Preventing Ventilator Associated Pneumonia in Neonatal Intensive Care Unit: A Cohort Study

Background: Despite improvement in overall survival, neonatal period is not free of complications. Ventilator associated Pneumonia (VAP) is a serious complication and account for 6.8 - 32.2 % of healthcare associated infections among neonates. Objective: The objective of the study was to document the effectiveness of an educational programme for neonatal intensive care (NICU) service provider in preventing occurrence of ventilator associated pneumonia in NICU. Methods: It was a prospective cohort study compared with historical control taken from the hospital records. All neonates admitted to the NICU during 12 months period from May 2019 to April 2020 were enrolled. Prospective enrollment of ventilated baby after educational interventions was subjected to the VAP educational care bundle. Eligible neonates who spent more than 48 h on MV were followed up and monitored closely for the development of VAP. Detail history, thorough clinical examination, relevant investigation including chest radiography were carried out on all enrolled infants. Results: A total of 54 neonates ventilated newborn, 41 met the inclusion criteria and were enrolled in the current study; 22 cases in pre-intervention phase and 19 cases in the post- intervention phase. Among enrolled mechanically ventilated newborn, 18 patients (18/41, 44%) developed at least single episode of VAP during the ventilated period. Baseline characteristics were comparable in both the groups. The primary indication of mechanical ventilation was sepsis related complications during both the phases (9/22, 41% and 8/19, 42.1%). Next to sepsis, perinatal asphyxia (5/22, 22.7%) was the indication of MV in pre-intervention period whereas respiratory distress syndrome (7/19, 36.8%) was the second leading causes of MV during post-intervention period. Significant reduction in VAP incidence rate was observed after implementation of VAP interventions, as 13/22, 59 % episodes of VAP were diagnosed in pre-intervention period compared to 5/19, 26.3% were diagnosed during implementation period. (p = 0.035). Non-significant reduction in mean duration of MV days was observed in the post-intervention period when compared to pre-intervention counterpart (7.23±4.48 days versus 5.16±2.77 days, p = 0.089). There was no significant reduction in NICU length of stay (13.05±8.16 versus 11.58±7.75 days in pre and post intervention period respectively, p = 0.56). The difference in overall mortality rates between the two phases were 15/22, 68.18% and 10/19, 52.63% respectively and found to be non- significant. Gram negative bacteria were the most commonly isolated micro-organisms, Acinetobacter was the leading causative pathogen. Conclusion: It demonstrates that an educational program including bundle of infection control practice can reduce the occurrence of VAP during ventilation period. These educational programs for NICU care providers can be expanded to other NICU s of the country to prevent ventilator associated pneumonia. Bangladesh Med Res Counc Bull 2021; 47(2): 143-150

The efficacy of fermented foods in the treatment and management of diarrhoeal diseases: A systematic review and meta-analysis.

Background: Diarrhoeal disease is a major cause of global infant mortality, and compromises the ability of many countries with respect to achieving sustainable development goals. The WHO's recommendation of Oral Rehydration Solution (ORS) and zinc in the management of this disease, may not be readily available. Consideration and assessment of cultural practices in its management has been an area of increased interest over the last decade. Aim: This study aims to systematically evaluate efficacy of the consumption of traditional fermented foods as functional products for the treatment and management of diarrhoea. Methods: Following PRISMA guidelines, a systematic review was conducted of electronic databases (Cochrane Library, Ovid Medline and Pubmed) databases with no restrictions on language and publication date for RCTs that investigated the effect of consumption of fermented foods on the treatment of diarrhoea in children under five years of age. Results: Seven RCTs were included. Meta-analysis showed that compared to control, consumption of fermented foods significantly reduced mean duration of diarrhoea, -0.61 days; (95% CI, -1.04, -0.18); length of hospitalization, -0.35 days (95% CI, -0.69, -0.02); but not mean daily frequency of stool -2.00 (95% CI,-7.03, 3.04). Conclusion: Limited available evidence suggests that consumption of fermented foods may help reduce duration and severity of symptoms as a treatment of diarrhoea. More high quality research needs to be undertaken to investigate the efficacy of fermented food as an effective alternative to ORS as a potential WHO recommendation for management of diarrhoeal disease.

A prospective randomized single blind study to compare the safety and efficacy of propronolol and topiramate in migraine prophylaxis

Background: The aim of the study was to compare the Safety and efficacy of propranolol and topiramate in migraine prophylaxis.Methods: This was a prospective, randomized, single blind study which was conducted for six months in 100 patients of outpatient department of Neurology Government General Hospital, Guntur.Results: Among the hundred patients fifty were allotted to group A – propranolol 40 mg bd and fifty were allotted to group B- topiramate 25 mg bd. statistically there is no significant differences were found between the treatment groups of Propranolol and topiramate for the reduction in mean duration and severity of migraine headaches. Both Propranolol and topiramate have p value<0.001. This shows that both propranolol and topiramate have significantly decreased in the mean duration and severity of migraine attacks. However, in the present study topiramate is slightly more efficacious in reducing the symptoms of migraine frequency per month (days), duration and severity (visual analogue scale- VAS score) from baseline at the end of six months. The decrease in frequency of migraine attacks from 10.44±4.38 to 3.18±4.48 i.e., 70.2% from baseline is seen with topiramate.Conclusions: This study demonstrated that both propranolol and topiramate could significantly reduce migraine headache frequency, duration and intensity. However, compared with propranolol topiramate showed better results. topiramate 25 mg reduced the symptoms like frequency, duration and severity of migraine attacks from base line at the end of six months but more number of adverse effects were seen in topiramate group.

Model of a Queuing Approach for Patient Accrual in Phase 1 Oncology Studies

Phase 1 cancer studies, which guide dose selection for subsequent studies, are almost 3 times more prevalent than phase 3 studies and have a median study duration considerably longer than 2 years, which constitutes a major component of drug development time. To discern a method to reduce the duration of phase 1 studies in adult and pediatric cancer studies without violating risk limits by better accommodating the accrual and evaluation process (or queue). The process modeled, the phase 1 queue (IQ), includes patient interarrival time, screening, and dose-limiting toxicity evaluation. For this proof of principle, the rules of the 3 + 3 and rolling 6 phase 1 designs were modified to improve patient flow through the queue without exceeding the maximum risk permitted in the parent designs. The resulting designs, the IQ 3 + 3 and the IQ rolling 6, were each compared with their parent design by simulations in 12 different scenarios. (1) The time from study opening to determination of the maximum tolerated dose (MTD), (2) the number of patients treated to determine the MTD, and (3) the association of the design with the dose selected as the MTD. Based on 800 simulations, for all 12 scenarios considered, the IQ 3 + 3 and the IQ rolling 6 designs were associated with reduced expected study durations compared with the parent design. The expected IQ 3 + 3 reduction ranged from 1.6 to 10.4 months (with 3.7 months for the standard scenario), and the expected reduction associated with IQ rolling 6 ranged from 0.4 to 10.5 months (with 3.4 months for the standard scenario). The increase in the mean number of patients treated in the IQ 3 + 3 compared with the 3 + 3 ranged from 0.6 to 3.2 patients. No increase in the number of patients was associated with the IQ rolling 6 compared with the rolling 6 design. The probability of selecting a dose level as the MTD changed by less than 3% for all dose levels and scenarios in both parent designs. This study found that IQ designs were associated with reduced mean duration of phase 1 studies compared with their parent designs without changing the risk limits or MTD selection operating characteristics. These approaches have been successfully implemented in both hematology and solid tumor phase 1 studies.

Learning Curve for Laparoscopic Hysterectomy: An Experience from Kathmandu University Hospital

Aims: The aim of this study is to assess learning curves for laparoscopic hysterectomies, compare the performance of surgeons and review demographic parameters of the patients, varieties of complications experienced and indications of the procedures.
 Methods: A retrospective study was conducted in Kathmandu University Hospital, Kavre of January 1, 2011 to June 30, 2018.
 Results: A total of 1849 cases were already performed by mid 2018. Of them, 261 (14.12%) cases were LAVH and TLH cases. Mean duration for laparoscopic hysterectomies (for both LAVH and TLH) was 142.21±43.46 minutes (range 55 to 310 minutes) and one third of the cases performed in a range of 121 to 150 minutes. There is difference in mean duration of operation between surgeons which is statistically significant (p <0.001). Beside one of four surgeons (surgeon B) had significant reduction in mean duration for LAVH surgery (p=0.004). Same surgeon has significant reduction in mean duration for performing TLH (p=0.0047). Of the 261 laparoscopic hysterectomies, 8 cases (3.07%) turned into laparotomy.
 Conclusions: Laparoscopic hysterectomies are feasible with reducing mean operating time across the period. These minimal invasive surgeries are safe with low rate of complications and less conversion to open even in our set up.

Early-life status epilepticus acutely impacts select quantitative and qualitative features of neonatal vocalization behavior: Spectrographic and temporal characterizations in C57BL/6 mice.

Early-life seizures are known to cause long-term deficits in social behavior, learning, and memory, however little is known regarding their acute impact. Ultrasonic vocalization (USV) recordings have been developed as a tool for investigating early communicative deficits in mice. Previous investigation from our lab found that postnatal day (PD) 10 seizures cause male-specific suppression of 50-kHz USVs on PD12 in 129 SvEvTac mouse pups. The present study extends these findings by spectrographic characterization of USVs following neonatal seizures. On PD10, male C57BL/6 pups were administered intraperitoneal injections of kainic acid or physiological saline. On PD12, isolation-induced recordings were captured using a broad-spectrum ultrasonic microphone. Status epilepticus significantly suppressed USV quantity (p=0.001) and total duration (p<0.05). Seizure pups also utilized fewer complex calls than controls (p<0.05). There were no changes in call latency or inter-call intervals. Spectrographic analysis revealed increased peak amplitude for complex, downward, short, two-syllable, and upward calls, as well as reduced mean duration for short and two-syllable calls in seizure mice. This investigation provides the first known spectrographic characterization of USVs following early-life seizures. These findings also enhance evidence for USVs as an indicator of select communicative impairment.

Psychopharmacological Evaluation of Alkaloidal Fraction of Desmodium gangeticum

Desmodium gangeticum D.C. (Salpani; family-Fabaceae) has been traditionally used as nervine tonic. Previous studies have shown antiamnesic activity of alkaloidal fraction (AF) of the plant. Thus, it was envisaged to subject AF (25 or 50 mg/kg, p.o.) for antianxiety, anticonvulsant, antidepressant, locomotor and hypnotic activities using well established models. AF exhibited significant antianxiety activity with respect to control using elevated plus maze model but the activity was not comparable to the standard drug, diazepam (2 mg/kg, p.o.). AF (50 mg/kg, p.o.) significantly reduced immobility time in forced swim test but did not stimulate locomotor activity of mice in open field test, suggesting its specific antidepressant activity. AF, at the doses of 25 and 50 mg/kg, reduced mean duration of tonic extensor phase to 15.25 and 14.55 sec, respectively, with respect to control (22.15 sec) but showed only 50% protection of mice from mortality due to maximal electroshock-induced convulsions. AF was found to be devoid of hypnotic activity as it could not potentiate duration of sleep in mice treated with thiopentone sodium. AF of D. gangeticum roots exerts mild CNS depression without causing sedation and possesses strong antidepressant activity.

Effect of Bilineaster Drop on Neonatal Hyperbilirubinemia

Background: Hyperbilirubinemia is considered one of the most prevalent problems in newborns. Phototherapy, exchange transfusion, and herbal medicine are common therapeutic approaches for preventing any neurologic damage in infants with neonatal jaundice. However, herbal medicine is less commonly used. Aim: This study aimed to investigate the effect of bilineaster drop on neonatal hyperbilirubinemia. Method: This study was a randomized clinical trial conducted on 98 term neonates (aged 2-14 days) with neonatal jaundice admitted to Ghaem Hospital of Mashhad, Iran, during 2015. These newborns were randomly assigned into intervention (phototherapy and bilineaster drop) and control (only phototherapy) groups. Total and direct serum bilirubin levels were measured at the time of admission and then 12, 24, 36, and 48 h after treatment. Data were analyzed using independent t-test and repeated measures ANOVA through Stata software (Version 12). Results: The mean ages of the newborns at the time of admission were 6.2 ±2.5 and 6.04 ±2.4 days in the intervention and control groups, respectively. The intervention group showed higher reduction in mean duration of hospital stay, readmission rate, and bilirubin levels 12 and 24 h after the intervention, compared to the control group (P>0.001). However, the two groups demonstrated no statistically significant difference 36 h and 48 h after the intervention (P=0.06, P=0.22, respectively). Repeated measures ANOVA indicated that the intervention had no significant effect on the reduction trend of bilirubin levels (P=0.10 [total], P=0.06 [indirect]) in both groups. Nonetheless, bilirubin levels significantly diminished in both groups over time (P<0.001). Implications for Practice: The results of this study demonstrated that the use of bilineaster drop along with phototherapy could cause a significant decrease in the levels of total and direct bilirubin; however, the intervention had no effect on the downward trend of bilirubin.

A study on the anticonvulsant activity of Withania somnifera (Dunal) in albino rats

Background: The present study is an investigation of antiepileptic activity of Withania somnifera (Ashwagandha) is a well-known plant which is being used in tuberculosis, emaciation, sterility, and it has immunomodulatory, anabolic, anti-inflammatory, and antianxiety activities. Aims and Objectives: To find the efficacy of the alcoholic extract of W. somnifera (Dunal) in preventing experimentally-induced seizures. Materials and Methods: The alcoholic extract of W. somnifera was subjected to pilot study and then screened for anticonvulsant activity on maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced seizures models in albino Wistar rats. Animals were treated with W. somnifera at doses of 100 mg/kg, 200 mg/kg, and 300 mg/kg body weight and compared the results with control and standard. Results: Study results showed that W. somnifera extract at the dose of 300 mg/kg body weight when compared to control group highly significant (P < 0.01) reduction of hindlimb tonic extension and postictal depression in MES. PTZ-induced seizures showed significantly reduced mean duration of hindlimb tonic flexion, hindlimb tonic extension, clonus, and stupor and there was no postictal depression. Conclusions: The alcoholic extract of W. somnifera (Dunal) has shown a significant anticonvulsant effect at the dose of 300 mg/kg body weight, both in MES method and PTZ method and has given higher protection rate against pentylenetetrazol seizure than MES.

A Comparative Study of Probiotic Lactic Acid Bacilli Alone and in Combination with Bifidobacterium and Saccharomyces as Adjuvants to ORS and Zinc in the Management of Acute Pediatric Diarrhoea

Introduction: Pediatric diarrhoea is the second leading cause of childhood mortality. It is a major global health problem, particularly affecting children under the age of 5 years. It is managed with oral rehydration salt, and zinc supplements. Recently, there has been a trend of prescribing probiotics which help in reducing the frequency and duration of diarrhoea. As India is fast emerging as a potential market for probiotics, scientific studies are required to ensure their efficacy. With this background, this study was undertaken to evaluate the role of probiotics in the treatment of acute onset mild and moderate pediatric diarrhea. Materials and Methods: This was an observational, prospective, open label, comparative study. It was conducted on 90 children after obtaining informed consent from their guardian. The participants were allocated to one of three study groups as follows; Group A: ORS & zinc Group, B: ORS, Zinc and lactic acid bacilli; Group C: ORS, Zinc and combination of lactic acid bacilli acidophilus, Bifidobacterium lactis and Saccharomyces boulardii. They were followed up for 72 hours after receiving the treatment and after 7 days. The outcome measures were reduction in mean duration and mean frequency of diarrhea. Data was collected in case report forms. Statistical analysis was done using ANOVA followed by Dunnet’s test. Results: The mean frequency of diarrhea on day 1 in Group A, B and C were 5.87±1.23; 6.5±1.15 and 6.63±1.42 respectively. On day 2, in Group A it was 2.93±0.82; Group B, 3.23±0.99 and in Group C, 2.73±0.89 respectively. On day 3, in Group A it was 1.33±0.47; Group B, 0.86±0.5 and in Group C, 0.53±0.5 respectively. The mean duration of diarrhea in Group A, B and C were 4.5±0.76, 3.47±0.5 and 3.17±0.37 days respectively. There was significant reduction in mean frequency and duration of diarrhea in Group B and C compared to Group A (p˂0.05). Conclusion: Probiotics when used alone or in combination as adjuvant to ORS and Zinc in the treatment of acute pediatric diarrhea results in significant reduction in mean frequency and mean duration of diarrhea.

WS13.3 A new combination of CFTR modulators corrects processing and reduces chronic inhibition for F508del-CFTR

Post-hoc analysis of a randomized, double-blind, placebo-controlled, phase 3 study showed a significant difference in relative change from baseline in %-predicted FEV1 favouring the ataluren-treated group vs placebo in patients not using chronic inhaled tobramycin (non-TOBI). As exacerbations are key drivers of disease progression, the effect of ataluren on exacerbations in nmCF patients was studied. Methods: A post-hoc analysis was conducted on the effect of ataluren on exacerbations, as defined by the modified Fuchs’ criteria, in nonTOBI patients (N=146). Rates and rate ratio were estimated using a generalized linear model. Results: In non-TOBI patients, there was a significant 40% reduction in mean exacerbation rate at 48 weeks for patients on ataluren vs placebo (Table). Of non-TOBI patients receiving placebo, 53 of 74 (72%) patients were not on any inhaled antibiotics at baseline. Median time to first pulmonary exacerbation was ±280 days for ataluren vs ±165 days for placebo. There was a 50.7% reduction in mean duration of hospitalization in non-TOBI patients on ataluren vs placebo (3.3 days for ataluren vs 6.5 days for placebo).

Effect of Different Concentration of Intraumblical Injection of Oxytocin and Saline on Third Stage of Labor

Objectives:The aim of study is to study the different concentration of intraumblical oxytocin saline injection on duration and blood loss of third stage of labor and other parameter. Methods:After considering inclusion and exclusion criteria, cases were divided in to 5 groups. All Women were injected 50 ml of normal saline into umbilical vein immediately after clamping and cutting the cord, in group A without oxytocin, in Group B with 10 units of oxytocin, in group C with 20 unit oxytocin and in group D with 30 unit oxytocin. In group E (control) women were managed conservatively. Duration and amount of blood loss of third stage was noted. Results: There were total 250 women enrolled in the study. A statistically significant reduction in the duration and amount of blood loss of third stage of labor was found in group B compared to group A. On increasing the concentration of oxytocin from 10 IU to 20 IU a slight reduction in mean duration and amount of blood loss of third stage was noted. On further increasing the concentration of oxytocin to 30 IU a statistical significant reduction was present. Conclusion: For active management of third stage intraumblical injection of oxytocin with saline should be promoted.

Running barbed suture quilting reduces abdominal drainage in perforator-based breast reconstruction

Prolonged abdominal drainage after perforator-based breast reconstruction is a common problem that can result in seroma formation, patient morbidity, and increased duration of hospital stay. Abdominal quilting with progressive tension sutures has been effective in reducing abdominal drainage in abdominoplasty patients prompting a change of practice in our unit. We studied consecutive unilateral mastectomy patients undergoing breast reconstruction with a deep inferior epigastric artery perforator (DIEP) flap. The initial 27 patients underwent breast reconstruction without any form of abdominal flap plication. The subsequent 26 patients underwent an identical DIEP flap raise procedure after which the abdominal flap was progressively tensioned using a running barbed suture quilting technique. All patients had closed suction drains inserted bilaterally until daily drain output was <40 ml in 2 consecutive days. Primary outcome measures were total volume of abdominal drainage and length of hospital stay. Independent statistical analyses were performed using Welch's t-test. There were no demographic differences between the two groups. A statistically significant decrease in the mean total abdominal drainage was found after quilting (238 ml vs. 528 ml; p = 0.0005). Patients in the quilting group also showed a reduction in mean duration of hospital stay. Quilting of the abdominal flap helps to reduce abdominal drainage not only in abdominoplasty patients but also in patients undergoing breast reconstruction with DIEP flap.

Zanamivir for influenza in adults and children: systematic review of clinical study reports and summary of regulatory comments

Objectives To describe the potential benefits and harms of zanamivir.Design Systematic review of clinical study reports of randomised placebo controlled trials and regulatory informationData sources Clinical study reports, trial registries,...

Unilateral approach for bilateral decompression of lumbar spinal stenosis: a minimal invasive surgery.

To assess the feasibility and efficacy of a novel, minimally invasive spinal surgery technique for the correction of lumbar spinal stenosis involving unilateral approach for bilateral decompression. Cross-sectional observational study. Neurosurgery Department of PGMI, Lady Reading Hospital, Peshawar, from January to December 2010. A total of 60 patients with lumbar stenosis were randomly assigned to undergo either a conventional laminectomy (30 patients, Group A), or a unilateral approach (30 patients, Group B). Clinical outcomes was measured using the scale of Finneson and Cooper. All the data was collected by using a proforma and different parameters were assessed for a minimum follow-up period of three months. Data was analyzed by descriptive statistics using SPSS software version 17. Adequate decompression was achieved in all patients. Compared with patients in the conventional laminectomy group, patients who received the novel procedure (unilateral approach) had a reduced mean duration of hospital stay, a faster recovery rate and majority of the patients (88.33%) had an excellent to fair operative result according to the Finneson and Cooper scale. Five major complications occurred in all patient groups, 2 patients had unintended dural rent and 2 wound dehiscence each and fifth patient had worsening of symptoms. There was no mortality in the series. The ultimate goal of the unilateral approach to treat lumbar spinal stenosis is to achieve adequate decompression of the neural elements. An additional benefit of a minimally invasive approach is adequate preservation of vertebral stability, as it requires only minimal muscle trauma, preservation of supraspinous/intraspinous ligament complex and spinous process, therefore, allows early mobilization. This also shortens the hospital stay, reduces postoperative back pain, and leads to satisfactory outcome.

Improving Safety of Preemptive Therapy with Oral Valganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Valganciclovir (VGC), an oral prodrug of ganciclovir (GCV), has been shown to clear cytomegalovirus (CMV) viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT), apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79%) than non-VGC therapies (69%). The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss) requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients), we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%), we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0–66)) compared to non-VGC (25 days (0–115)), without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity.

Treating and Preventing Influenza in Aged Care Facilities: A Cluster Randomised Controlled Trial

BackgroundInfluenza is an important cause of morbidity and mortality for frail older people. Whilst the antiviral drug oseltamivir (a neuraminidase inhibitor) is approved for treatment and prophylaxis of influenza during outbreaks, there have been no trials comparing treatment only (T) versus treatment and prophylaxis (T&P) in Aged Care Facilities (ACFs). Our objective was to compare a policy of T versus T&P for influenza outbreaks in ACFs.Methods and FindingsWe performed a cluster randomised controlled trial in 16 ACFs, that followed a policy of either “T”—oseltamivir treatment (75 mg twice a day for 5 days)—or “T&P”—treatment and prophylaxis (75 mg once a day for 10 days) for influenza outbreaks over three years, in addition to enhanced surveillance. The primary outcome measure was the attack rate of influenza. Secondary outcomes measures were deaths, hospitalisation, pneumonia and adverse events. Laboratory testing was performed to identify the viral cause of influenza-like illness (ILI) outbreaks. The study period 30 June 2006 to 23 December 2008 included three southern hemisphere winters. During that time, influenza was confirmed as the cause of nine of the 23 ILI outbreaks that occurred amongst the 16 ACFs. The policy of T&P resulted in a significant reduction in the influenza attack rate amongst residents: 93/255 (36%) in residents in T facilities versus 91/397 (23%) in T&P facilities (p = 0.002). We observed a non-significant reduction in staff: 46/216 (21%) in T facilities versus 47/350 (13%) in T&P facilities (p = 0.5). There was a significant reduction in mean duration of outbreaks (T = 24 days, T&P = 11 days, p = 0.04). Deaths, hospitalisations and pneumonia were non-significantly reduced in the T&P allocated facilities. Drug adverse events were common but tolerated.ConclusionOur trial lacked power but these results provide some support for a policy of “treatment and prophylaxis” with oseltamivir in controlling influenza outbreaks in ACFs.Trail RegistrationAustralian Clinical Trials Registry ACTRN12606000278538

Anatomical dissociation of melanocortin receptor agonist effects on taste- and gut-sensitive feeding processes

Injections of the melanocortin 3/4 receptor (MCR) agonist melanotan II (MTII) to a variety of brain structures produces anorexia, suggesting distributed brain MCR control of food intake. We performed a detailed analysis of feeding behavior (licking microstructure analysis) after a range of MTII doses (0.005 nM to 1 nM) was targeted to the forebrain (third ventricle, 3V) or hindbrain (fourth ventricle, 4V) regions. MTII (0.1 nM and 1 nM) delivered to the 3V or 4V significantly reduced 0.8 M sucrose intake. The anorexia was mediated by reductions in the number of licking bursts in the meal, intrameal ingestion rate, and meal duration; these measures have been associated with postingestive feedback inhibition of feeding. Anorexia after 3V but not 4V MTII injection was also associated with a reduced rate of licking in the first minute (initial lick rate) and reduced mean duration of licking bursts; these measures have been associated with taste evaluation. MTII effects on taste evaluation were further explored: In experiment 2, 3V MTII (1 nM) significantly reduced intake of noncaloric 4 mM saccharin and 0.1 M and 1 M sucrose solutions, but not water. The anorexia was again associated with reduced number of licking bursts, ingestion rate, meal duration, initial lick rate, and mean burst duration. In experiments 3 and 4, brief access (20 s) licking responses for sweet sucrose (0.015 M to 0.25 M) and bitter quinine hydrochloride (0.01 mM to 1 mM) solutions were evaluated. Licking responses for sucrose were suppressed, whereas those for quinine solutions were increased after 3V MTII, but not after 4V MTII injections (0.1 nM and 1 nM). The results suggest that multiple brain MCR sites influence sensitivity to visceral feedback, whereas forebrain MCR stimulation is necessary to influence taste responsiveness, possibly through attenuation of the perceived intensity of taste stimuli.