Search PubMed⌕ Search

Biomedical subjects

S Shah

Publications and source records attributed to S Shah.

At least 37 records · Page 2Linked to original sources
PubMed2004

Interleukin 1beta enhances non-rapid eye movement sleep and increases c-Fos protein expression in the median preoptic nucleus of the hypothalamus.

Interleukin 1beta (IL-1) is a key mediator of the acute phase response in an infected host and acts centrally to coordinate responses to an immune challenge, such as fever and increased non-rapid eye movement (NREM) sleep. The preoptic area (POA) is a primary sleep regulatory center in the brain: the ventrolateral POA (VLPO) and median preoptic nucleus (MnPN) each contain high numbers of c-Fos protein immunoreactive (IR) neurons after sleep but not after waking. We hypothesized that IL-1 mediates increased NREM sleep through activation of these sleep-active sites. Rats injected intracerebroventricularly with IL-1 (10 ng) at dark onset spent significantly more time in NREM sleep 4-5 h after injection. This increase in NREM sleep was associated with increased numbers of Fos-IR neurons in the MnPN, but not in the VLPO. Fos IR in the rostral MnPN was significantly increased 2 h post IL-1 injection, although the percentage of NREM sleep in the preceding 2 h was the same as controls. Fos IR was also increased in the extended VLPO 2 h postinjection. Finally, Fos IR in the MnPN did not differ significantly between IL-1 and vehicle-treated rats that had been sleep deprived for 2 h postinjection, but it was increased in VLPO core. Taken together, these results suggest that Fos IR in the MnPN after IL-1 is not independent of behavioral state and may require some threshold amount of sleep for its expression. Our results support a hypothesis that IL-1 enhances NREM sleep, in part, through activation of neurons in the MnPN of the hypothalamus.

Animals↗
PubMed2004

Natural history of nonketotic hyperglycinemia in 65 patients.

BACKGROUND: Glycine encephalopathy, also known as nonketotic hyperglycinemia (NKH), is an autosomal recessive disorder caused by a defect in the glycine cleavage system. NKH is classically associated with neonatal apnea, lethargy, hypotonia, and seizures, followed by severe psychomotor retardation in those who survive. METHODS: To determine the natural history of NKH, the authors mailed a 44-question survey to 170 households in the International NKH Family Network. RESULTS: Data for 65 patients (36 boys, 29 girls) were collected from 58 families. One-third of the subjects died; 8 girls died during the neonatal period, and 14 patients died thereafter (2 girls, 12 boys). Median age of death for boys was 2.6 years vs <1 month for girls (p = 0.02). Mean birth weight and length, occipitofrontal circumference, and gestation duration were normal. Two-thirds of infants were ventilated during the neonatal period; of these, 40% died. Ninety percent had confirmed seizures, 75% during the first month of life. Interestingly, three NKH patients never developed seizures. An abnormal corpus callosum and/or hydrocephalus were associated with especially poor gross motor and speech development. Of 25 patients living > or =3 years, 10 were able to walk and say/sign words; all were boys. In six families with more than one affected child, disease course and mortality were similar within each family. CONCLUSIONS: This study reveals a striking and unexpected gender difference in mortality and developmental progress. Of the two-thirds of nonketotic hyperglycinemia patients surviving the newborn period, up to 20% (mostly boys) may learn to walk and communicate by saying or signing words.

Adolescent↗
PubMed2004

Intraventricular antibiotics for bacterial meningitis in neonates.

BACKGROUND: Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm. OBJECTIVES: To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone. SEARCH STRATEGY: MEDLINE, EMBASE, The Cochrane Library, Issue 2, 2004, Science Citation Index, and the Oxford Database of Perinatal Trials were searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 - April 2004) as were reference lists of identified trials and personal files. No language restrictions were applied. SELECTION CRITERIA: Selection criteria for study inclusion were: Randomized or quasi-randomized controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalization, neonatal and/or infant mortality, neurodevelopmental outcome, duration of hospitalization, duration of culture positivity of CSF and side effects. DATA COLLECTION AND ANALYSIS: All reviewers abstracted information for outcomes reported and one reviewer checked for discrepancies and entered data into RevMan 4.2. Relative risk (RR), risk difference (RD), number needed to treat (NNT) or number needed to harm (NNH), and mean difference (MD), using the fixed effects model are reported with 95% confidence intervals (CI). The fixed effect model was used for meta-analysis. MAIN RESULTS: One study was included in the review. This study assessed the effect of intraventricular gentamicin in a mixed population of neonates (69%) and older infants (31%) with gram negative meningitis and ventriculitis. Mortality was statistically significantly higher in the group that received intraventricular gentamicin in addition to intravenous antibiotics compared to the group receiving intravenous antibiotics alone [RR 3.43 (95% CI, 1.09, 10.74; RD 0.30 (95% CI, 0.08, 0.53); NNH was 3 (95% CI; 2 ,13)]. Duration of CSF culture positivity did not differ significantly (MD -1.20 days (95% CI, -2.67, 0.27). REVIEWERS' CONCLUSIONS: In one trial, enrolling infants with gram negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a 3 fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.

Anti-Bacterial Agents↗
PubMed2004

Economic evaluation of donepezil in moderate to severe Alzheimer disease.

OBJECTIVE: To investigate the costs to society of Alzheimer disease (AD) care in a multinational, randomized, placebo-controlled trial of donepezil in patients with moderate to severe AD. METHODS: A total of 290 patients with AD (screening standardized Mini-Mental State Examination score 5 to 17) were randomized to receive either donepezil (n = 144; 5 mg/day for 28 days, followed by 10 mg/day as per clinician's judgment) or placebo (n = 146) for 24 weeks. The authors collected data on patient and caregiver health resource utilization prospectively using the Canadian Utilization of Services Tracking questionnaire. Costs were calculated for patients and caregivers in each group based on resource utilization multiplied by the unit prices for each resource. A cost (the average Ontario minimum wage for 1998 [Can 6.85 dollars per hour]) was assigned to unpaid time that caregivers spent assisting the patient with activities of daily living (ADL). RESULTS: Patient and caregiver demographics at baseline were similar across the two groups. After adjusting for baseline total cost per patient, the mean total societal cost per patient for the 24-week period was donepezil, Can 9,904 dollars (US 6,686 dollars) and placebo, Can 10,236 dollars (US 6,910 dollars). This net cost saving of Can 332 dollars (US 224 dollars) included the average 24-week cost of donepezil treatment. Most of the cost-saving with donepezil treatment was due to less use of residential care by patients, and caregivers spending less time assisting patients with ADL. CONCLUSION: This cost-consequence analysis reveals economic benefits of treatment of moderate to severe AD with donepezil.

Activities of Daily Living↗
PubMed2004

Transient evolution of surface roughness on patterned GaAs(001) during homoepitaxial growth.

We have investigated the length scale dependence of the transient evolution of surface roughness during homoepitaxial growth on GaAs(100), patterning the surface lithographically with an array of cylindrical pits of systematically varied sizes and spacings. Our atomic force microscopy measurements show that the amplitude of the surface corrugation has nonmonotonic behavior in both the length scale dependence and time evolution. This behavior allows us to rule out a number of existing continuum models of growth.

Journal Article↗
PubMed2004

Corneal pachymetry in normal and keratoconic eyes: Orbscan II versus ultrasound.

PURPOSE: To compare corneal thickness measurements using Orbscan II (OII) and ultrasonic (US) pachymetry in normal and in keratoconic eyes. SETTING: Eye Department, Heartlands and Solihull NHS Trust, Birmingham, United Kingdom. METHODS: Central corneal thickness (CCT) was measured by means of OII and US pachymetry in 1 eye of 72 normal subjects and 36 keratoconus patients. The apical corneal thickness (ACT) in keratoconus patients was also evaluated using each method. The mean of the difference, standard deviation (SD), and 95% limits of agreement (LoA = mean +/- 2 SD), with and without applying the default linear correction factor (LCF), were determined for each sample. The Student t test was used to identify significant differences between methods, and the correlation between methods was determined using the Pearson bivariate correlation. Bland-Altman analysis was performed to confirm that the results of the 2 instruments were clinically comparable. RESULTS: In normal eyes, the mean difference (+/- 95% LoA) in CCT was 1.04 microm +/- 68.52 (SD) (P>.05; r = 0.71) when the LCF was used and 46.73 +/- 75.40 microm (P =.0001; r = 0.71) without the LCF. In keratoconus patients, the mean difference (+/- 95% LoA) in CCT between methods was 42.46 +/- 66.56 microm (P<.0001: r = 0.85) with the LCF, and 2.51 +/- 73.00 microm (P>.05: r = 0.85) without the LCF. The mean difference (+/- 95% LoA) in ACT for this group was 49.24 +/- 60.88 microm (P<.0001: r = 0.89) with the LCF and 12.71 +/- 68.14 microm (P =.0077; r = 0.89) when the LCF was not used. CONCLUSIONS: This study suggests that OII and US pachymetry provide similar readings for CCT in normal subjects when an LCF is used. In keratoconus patients, OII provides a valid clinical tool for the noninvasive assessment of CCT when the LCF is not applied.

Adult↗
PubMed2004

Real time TaqMan PCR detection and quantitation of HBV genotypes A-G with the use of an internal quantitation standard.

BACKGROUND: Diagnostic assays for the accurate quantitation of hepatitis B virus (HBV) DNA levels from patients undergoing antiviral therapy are useful for monitoring and tailoring therapy. Such assays should give accurate results with all HBV genotypes, including a seventh genotype of hepatitis B virus, genotype G, that has recently been identified in specimens from HBV-positive patients in the United States and Europe. OBJECTIVES: To characterize the performance characteristics of a quantitative real time TaqMan PCR assay, the High Pure System Viral Nucleic Acid/COBAS TaqMan HBV Test, for the detection and quantitation of HBV genotypes A-G from patient plasma and serum. This test was evaluated for limit of detection, dynamic range, reproducibility, accuracy, and genotype inclusivity. STUDY DESIGN: Primers and TaqMan probes specific for HBV and an internal quantitation standard (QS) were designed and tested using a set of plasmid DNAs representing various genotyped specimens. In addition, sensitivity, dynamic range, precision, and correlation with the COBAS AMPLICOR HBV MONITOR Test were evaluated using HBV dilution panels and patient specimens. RESULTS AND CONCLUSIONS: A real time TaqMan assay was developed that detects and quantifies DNA from genotypes A-G equivalently. The assay has a limit of detection of <50 copies/ml with plasma and serum, a dynamic range up to 10(9) copies/ml, and good precision and accuracy. Titers obtained with this method without dilutions show good correlation across the dynamic range with titers obtained with the COBAS AMPLICOR HBV MONITOR Test.

DNA Primers↗
PubMed2004

Attitudes towards the use of hand over mouth (HOM) and physical restraint amongst paediatric specialist practitioners in the UK.

PURPOSE: To assess the views of paediatric specialist dental practitioners in the United Kingdom of the use of the hand over mouth technique and physical restraint. METHODS: Questionnaire survey of all specialist dental practitioners in paediatric dentistry in the United Kingdom (n = 216). Replies were received from 179 individuals (82.8%). RESULTS: The majority of the sample (over 80%) described HOM as having three components, broadly mirroring the description of the technique in clinical textbooks. Approximately 60% of the respondents reported that HOM should never be used (106 individuals, 59.2%). Those who endorsed the use of HOM suggested it should be used with cases of hysterical, tantrum behaviour (57 respondents, 32%). The use of physical restraint was endorsed for certain disabled patients by 110 individuals (62%); for very young patients by 69 respondents (39%); premedicated patients by 35 respondents (20%); physically resistive patients by 25 respondents (14%). Forty-three respondents (24%) felt there were no psychological consequences of the use of HOM or physical restraint; 91 (51%) felt that HOM would result in the child fearing dental treatment. CONCLUSIONS: Specialist paediatric dental practitioners in the UK are familiar with the technique of HOM although they also feel that this technique should never be used. A large proportion of practitioners felt that the use of physical restraint was appropriate with certain disabled patients. The most commonly anticipated psychological sequeala which may accompany the use of these techniques was subsequent fear of dental treatment.

Attitude of Health Personnel↗
PubMed2004

The effect of corneal thickness on intraocular pressure measurement in patients with corneal pathology.

BACKGROUND/AIM: To compare intraocular pressure (IOP) measurements taken by the Goldmann applanation tonometer, the Tono-Pen and the ocular blood flow pneumotonometer in eyes with varying central corneal thickness (CCT) due to penetrating keratoplasty (PK), keratoconus (KC), and Fuchs' endothelial dystrophy (FED). METHODS: IOP was measured with the Goldmann applanation tonometer, Tono-Pen XL, and OBF pneumotonometer in 127 eyes with the following corneal abnormalities. There were 56 eyes that had undergone PK, 37 eyes with KC, and 34 eyes with FED. CCT was measured using an ultrasound pachymeter after IOP determinations had been made. RESULTS: Mean IOP measurements in all three patient groups were significantly higher when measured by OBF pneumotonometer. Linear regression analysis showed that patients with FED had a significant increase in IOP with increasing CCT of 0.18 mm Hg/10 microm using the Goldmann tonometer, 0.15 mm Hg/10 microm with the Tono-Pen, and 0.26 mm Hg/10 microm with the OBF pneumotonometer. In patients with KC and after PK, linear regression analysis did not show a significant effect of CCT on IOP. A multivariate linear regression model controlling for age, sex, graft size, and patient group, showed that the effect of CCT on IOP for Tono-Pen (0.13 mm Hg/10 microm CCT) and Goldmann (0.14 mm Hg/10 microm CCT) were significantly lower than for the OBF pneumotonometer (0.26 mm Hg/10 microm CCT). CONCLUSIONS: This study found that mean IOP measurements using the OBF pneumotonometer were significantly higher than those made using the Goldmann applanation tonometer or Tono-Pen in eyes with a variety of cornel pathologies. The OBF pneumotonometer was found to be most affected by variation in CCT. For all three instruments, the relation between IOP and CCT depended on the corneal pathology and was greatest for FED.

Aged↗
PubMed2004

Management of chronic heart failure in the community: role of a hospital based open access heart failure service.

OBJECTIVE: To evaluate the role of an open access heart failure service based at a teaching hospital for the diagnosis and treatment optimisation of patients with heart failure in the community and to identify measures that may further enhance the effectiveness of such a service. SUBJECTS: 963 patients with suspected heart failure seen over an eight year period referred by their general practitioners to the cardiology department at a district general hospital. MAIN OUTCOME MEASURES: Presence or absence of left ventricular systolic dysfunction (LVSD) (left ventricular ejection fraction < 50% on echocardiography), and determination of the risk factors and predictors of LVSD. RESULTS: The majority of the patients were women (60% v 40%) and elderly (mean age 68.8 years). On echocardiography, only 30.8% were found to have LVSD. Patients were more likely to have LVSD if they were men (42.3% v 23.1%, p < 0.001, relative risk (RR) 1.8), were > 60 years of age (33.5% v 20.8%, p < 0.001, RR 1.6), or had a history of diabetes (49.4% v 29.1%, p < 0.001, RR 1.7), ischaemic heart disease (36.5% v 29.1%, p = 0.04, RR 1.3), or atrial fibrillation (52.6% v 27.8%, p < 0.001, RR 1.9). An abnormal ECG (48.4% v 19.5%, p < 0.001, RR 2.5) and cardiothoracic ratio > 0.5 on chest radiograph (44.3% v 17.8%, p < 0.001, RR 2.5) were found to be good predictors of LVSD. A normal ECG (negative predictive value 80.5%) and a cardiothoracic ratio of < 0.5 (negative predictive value 82.2%) can be used as baseline measures to identify patients with lower risk of developing LVSD (combined negative predictive value 87.9%). CONCLUSIONS: An open access heart failure clinic is effective for the diagnosis and management of chronic heart failure in community based patients. The presence of risk factors and simple baseline tests can be used to identify patients with LVSD in the community. The introduction of a protocol based on these findings into a referral system can improve the efficiency and cost effectiveness of such a service.

Aged↗
PubMed2004

A retrospective study of the association between haematological and biochemical parameters and morphine intolerance in patients with cancer pain.

BACKGROUND: Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines of the World Health Organization (WHO). However, a minority of patients do not receive the desired analgesic effect or suffer intolerable side effects from morphine, and are switched to alternative opioids. METHODS: The aim of this retrospective study was to identify factors that might be associated with morphine intolerance. Data were analysed from 100 controls who tolerated morphine and 77 patients who were switched to an alternative opioid. We investigated whether currently logged data could fully explain the need to switch. Demographic details, cancer type (histological diagnosis) and markers related to organ function were included in an analysis of biochemical and haematological parameters. RESULTS: Patients over 78 years (P = 0.03), or with a high white cell (P = 0.002) or high platelet count (P = 0.003), were more likely to switch. Although our numbers were small, patients with severe organ impairment were more likely to switch. However, a model including white cell count, platelet count, age, serum albumin and alkaline phosphatase, accurately separated switchers and controls in only 68% of cases. There was no significant difference between the two groups in terms of the numbers of patients having cytotoxic drugs in the two weeks prior to the haematological and biochemical analysis. Similarly, there were no significant differences in histological diagnoses between groups. CONCLUSIONS: The white cell count was the strongest single effect observed and, as such, warrants further investigation. Further studies are needed in order to accurately define a model that will predict those patients likely to be intolerant of morphine.

Aged↗
PubMed2004

Breakthrough pain characteristics and syndromes in patients with cancer pain. An international survey.

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Analysis of Variance↗
PubMed2003

Exploring dental patients' preferred roles in treatment decision-making - a novel approach.

AIMS: To assess the transferability of the Control Preferences Scale to dental settings and to explore patients' preferred and perceived roles in dental treatment decision-making. SETTING AND PARTICIPANTS: A convenience sample of 40 patients, 20 recruited from the University Dental Hospital of Manchester and 20 from a general dental practice in Cheshire. METHODS: A cross-sectional survey, using the Control Preferences Scale, a set of sort cards outlining five decisional roles (active, semi-active, collaborative, semi-passive, passive), slightly modified for use in dental settings. A second set of cards was used to identify perceived decisional role. Rationale for choice of preferred role was recorded verbatim. RESULTS: The Control Preferences Scale was found to be transferable to dental settings. All patients in the sample had identifiable preferences regarding their role in treatment decision-making. A collaborative decisional role, with patient and dentist equally sharing responsibility for decision-making, was most popular at both sites. However, patients at both sites typically perceived themselves as attaining a passive role in treatment decisions. Lack of knowledge about dentistry and trust in the dentist were reported contributors to a passive decisional role preference, whilst those with more active role preferences gave rationales consistent with a consumerist stance. CONCLUSIONS: This exploratory study's findings suggest that dental patients have distinct preferences in relation to treatment decision-making role and that these may not always be met during consultations with their dentist. The Control Preferences Scale appears to be appropriate for use in dental settings.

Adult↗
PubMed2003

Speciation of mercury in soil and sediment by selective solvent and acid extraction.

In order to characterize the mercury hazard in soil, a sequential extraction scheme has been developed to classify mercury species based on their environmental mobility and/or toxicity for either routine lab analysis or on-site screening purposes. The alkyl mercury species and soluble inorganic species that contribute to the major portion of potential mercury toxicity in the soil are extracted by an acidic ethanol solution (2% HCl+10% ethanol solution) from soil matrices as "mobile and toxic" species. A High-Performance Liquid Chromatography (HPLC) system coupled with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) detection has been developed to further resolve the species information into soluble inorganic species (Hg(2+)), methylmercury(II) (MeHg(+)) and ethylmercury(II) (EtHg(+)) species. Alternatively, these species can be separated into "soluble inorganic mercury" and "alkyl mercury" sub-categories by Solid-Phase Extraction (SPE). A custom Sulfydryl Cotton Fiber (SCF) material is used as the solid phase medium. Optimization of the SCF SPE technique is discussed. Combined with a direct mercury analyzer (DMA-80), the SCF SPE technique is a promising candidate for on-site screening purposes. Following the ethanol extraction, the inorganic mercury species remaining in soil are further divided into "semi-mobile" and "non-mobile" sub-categories by sequential acid extractions. The "semi-mobile" mercury species include mainly elemental mercury (Hg) and mercury-metal amalgams. The non-mobile mercury species mainly include mercuric sulfide (HgS) and mercurous chloride (Hg(2)Cl(2)).

Chemical Fractionation↗
PubMed2003

Ibuprofen for the treatment of a patent ductus arteriosus in preterm and/or low birth weight infants.

BACKGROUND: A patent ductus arteriosus (PDA) complicates the clinical course of preterm infants, increasing their risks of developing chronic lung disease (CLD), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH). Indomethacin is used as standard therapy to close a PDA, but is associated with reduced blood flow to the brain, kidneys and gut. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective with fewer side effects. OBJECTIVES: To determine the effectiveness and safety of ibuprofen compared to placebo or no intervention for closing a PDA in preterm and/or low birth weight infants. To determine the effectiveness and safety of ibuprofen compared to other cyclo-oxygenase inhibitors (including indomethacin, mefenamic acid) for closing a PDA in preterm and/or low birth weight infants. SEARCH STRATEGY: Randomized (or quasi-randomized) controlled trials (RCTs) comparing ibuprofen to placebo or indomethacin or mefenamic acid for therapy of PDA were identified by searching the Cochrane Controlled Trials Register (Issue 4, 2002), MEDLINE (1996 - January 2003), CINAHL (1982 - November 2002), EMBASE (1980 - January 2002), reference lists of published RCTs and abstracts from the Pediatric Academic Societies and the European Society for Pediatric Research meetings published in Pediatric Research (1991 - 2002). No language restrictions were applied. SELECTION CRITERIA: 1) DESIGN: Randomized or quasi-randomized controlled trials 2) POPULATION: Preterm (< 37 weeks gestational age) or low birth weight infants (< 2500 grams) with a clinically or echocardiographically diagnosed PDA 3) INTERVENTION: Administration of ibuprofen for the closure of PDA 4) OUTCOMES: At least one of the following outcomes were reported: failure to close a PDA, mortality, surgical ligation, intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), NEC, decreased urine output, retinopathy of prematurity (ROP), CLD, sepsis, days on supplementary oxygen. DATA COLLECTION AND ANALYSIS: At least two reviewers worked independently at each step of the review, then compared results and resolved differences. Methodological quality of eligible studies was assessed according to blinding of randomization, of intervention and of outcome assessment, and completeness of followup. Weighted treatment effects, calculated using Revman 4.1, included typical relative risk (RR), typical risk difference (RD), number needed to treat (NNT) or harm (NNH), and weighted mean difference (WMD), all with 95% confidence intervals (CI). A fixed effect model was used for meta-analyses. Heterogeneity tests were performed to assess the appropriateness of pooling the data. MAIN RESULTS: Eight studies including 509 patients were included. All studies compared the effectiveness of ibuprofen to indomethacin for the closure of a PDA. There was no statistically significant heterogeneity of treatment effect for any of the outcomes. For the primary outcome (failure of ductal closure), there was no statistically significant difference between ibuprofen and indomethacin groups [RR 0.92 (95% CI 0.69, 1.22)]. There were no statistically significant differences in mortality, surgical duct ligation, duration of ventilator support, IVH, PVL, NEC, time to full enteral feeds, ROP, sepsis, duration of hospital stay or gastrointestinal bleed. For many of these outcomes the sample size was small and the estimates imprecise. The incidence of decreased urine output (< 1cc/kg/hr) was lower in the ibuprofen group as compared to the indomethacin group [NNT 9 (95% CI 5-14)]. This was the only statistically significant clinical finding favouring ibuprofen. Chronic lung disease defined as oxygen requirement at 28 days post-natally was statistically significantly more likely to occur in the ibuprofen group [RR 1.37 (95% CI 1.01, 1.86); NNH 7 (95% CI 3 - 100)]. No studies comparing ibuprofen versus placebo for the closure of PDA were identified. REVIEWER'S CONCLUSIONS: We found no statistically significant difference in the effectiveness of ibuprofen compared to indomethacin in closing the PDA. Ibuprofen reduces the risk of oliguria. However, ibuprofen may increase the risk for chronic lung disease, and pulmonary hypertension has been observed in three infants after prophylactic use of ibuprofen. Based on currently available information ibuprofen does not appear to confer a net benefit over indomethacin for the treatment of a PDA. We conclude that indomethacin should remain the drug of choice for the treatment of a PDA. Future research may include a four arm trial where infants are randomized at birth, either to a prophylaxis arm starting at birth or to an arm in which treatment starts after a PDA is diagnosed by echocardiography within the first seven days of life. Within the prophylaxis and treatment arms, the infants would be randomized to either ibuprofen or indomethacin. The primary outcome should be intact survival (survival without handicap) at 18 months corrected age.

Cyclooxygenase Inhibitors↗
PubMed2003

Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants.

BACKGROUND: Patent ductus arteriosus (PDA) with significant left to right shunt in preterm infants increases morbidity and mortality. Early closure of the ductus arteriosus may be achieved pharmacologically using cyclooxygenase inhibitors, or by surgery. The efficacy of both treatment modalities is well established. However, the preferred initial treatment of a symptomatic PDA in a preterm infant, surgical ligation or trial of indomethacin, has not been well established. OBJECTIVES: To compare the effect of surgical ligation of PDA versus medical treatment with cyclooxygenase inhibitors (using indomethacin, ibuprofen, or mefenamic acid), each used as the initial treatment, on neonatal mortality in preterm infants with a symptomatic PDA. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included search of electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), MEDLINE (1966 - December 2002), CINAHL (1982 - December 2002), EMBASE (1980 - December 2002); and hand search of abstracts of Pediatric Academic Societies annual meetings published in Pediatric Research (1990 - April 2002). No language restrictions were applied. SELECTION CRITERIA: All trials 1) using randomized or quasi-randomized patient allocation, 2) in preterm infants < 37 weeks gestational age or low-birth-weight infants (< 2500 grams) with symptomatic PDA in the neonatal period (< 28 days) and 3) comparing surgical ligation with medical treatment with cyclooxygenase inhibitors, each used as the initial treatment for closure of PDA. DATA COLLECTION AND ANALYSIS: Assessment of methodological quality and extraction of data for included trials was undertaken independently by the authors. RevMan 4.1 was used for analysis of the data. MAIN RESULTS: Only one study, trial B in the report of Gersony 1983, was found eligible. The trial compared the effect of surgical ligation of PDA versus medical treatment with indomethacin, each used as the primary treatment. No trials comparing surgery to other cyclooxygenase inhibitors (ibuprofen, mefenamic acid) were found. Trial B of Gersony 1983 enrolled 154 infants. The study found no statistically significant difference between surgical closure and indomethacin treatment in mortality during hospital stay, chronic lung disease, other bleeding, necrotizing enterocolitis, sepsis, creatinine level, or intraventricular hemorrhage. There was a statistically significant increase in the surgical group in incidence of pneumothorax [RR 2.68 (95% CI 1.45, 4.93); RD 0.25 (95% CI 0.11, 0.38); NNH 4 (95% CI 3, 9)] and retinopathy of prematurity grade III and IV [RR 3.80 (95% CI 1.12, 12.93); RD 0.11 (95% CI 0.02, 0.20), NNH 9 (95% CI 5, 50] compared to the indomethacin group. There was as expected a statistically significant decrease in failure of ductal closure rate in the surgical group as compared to the indomethacin group: [RR 0.04 (95% CI 0.01, 0.27); RD -0.32 (95% CI -0.43, -0.21), NNT 3 (95% CI 2, 4)]. REVIEWER'S CONCLUSIONS: The data regarding net benefit/harm are insufficient to make a conclusion as to whether surgical ligation or medical treatment with indomethacin is preferred as initial treatment for symptomatic PDA in preterm infants.

Cyclooxygenase Inhibitors↗
PubMed2003

End-of-life decision making--have we got it right?

There are wide-spread misconceptions about palliative care. Various treatments used in palliative care have a potential to shorten, and at times even prolong life. However, such treatments are used with a view to enhance quality of life and/or death. Withholding and withdrawal of life-prolonging treatments are not equivalent to assisting death. It is important that patients who are approaching death are sensitively encouraged to make informed choices about such treatments. At the same time, there is no obligation on part of a health professional to provide a futile treatment. This personal view of two palliative care physicians aims to explore some of the difficulties surrounding end-of-life care.

Decision Making↗