A meta-analysis to assess usefulness of procalcitonin-guided antibiotic usage for decision making.

BACKGROUND & OBJECTIVES: Development of antibacterial resistance and its association with antibiotic overuse makes it necessary to identify a specific and sensitive biomarker for the diagnosis of bacterial infection and guiding antibiotic therapy. Procalcitonin (PCT), as a sepsis biomarker, may play a role in guiding antibiotics treatment in hospital settings. The aim of the current meta-analysis was to analyze the utility of PCT on various outcomes of interest in inpatients. METHODS: Different databases were searched for randomized controlled trials comparing PCT-guided therapy with standard therapy in admitted patients with bacterial infections. Twenty six articles were found suitable for full text search and of these, 16 studies were considered finally for data extraction. RESULTS: There were no significant differences found in total mortality [pooled odds ratio (OR) 1.04, 95% confidence interval (CI) 0.89-1.22, P=0.63], 28-day mortality (pooled OR 0.97, 95% CI 0.80-1.19, P=0.79), need of Intensive Care Unit admission (OR=0.80, 95% CI 0.59-1.09, P=0.16) and duration of stay in hospital (pooled mean difference -0.01, 95% CI -0.50-0.49, P=0.98) between treatment and control groups. PCT-guided treatment significantly decreased the duration of antibiotic treatment (pooled mean difference -2.79, 95% CI -3.52--2.06, P<0.00001). INTERPRETATION & CONCLUSIONS: PCT-guided therapy significantly decreased antibiotics exposure and thus treatment cost. However, the hard endpoints did not demonstrate any significant benefits, possibly due to low power to detect differences and/or the presence of comorbidities.

Dietary treatment for familial hypercholesterolaemia.

BACKGROUND: A cholesterol-lowering diet and several other dietary interventions have been suggested as a management approach either independently or as an adjuvant to drug therapy in children and adults with familial hypercholesterolemia. However, a consensus has yet to be reached on the most appropriate dietary treatment. OBJECTIVES: To examine whether a cholesterol-lowering diet is more effective in reducing ischaemic heart disease and lowering cholesterol than no dietary intervention in children and adults with familial hypercholesterolaemia. Further, to compare the efficacy of supplementing a cholesterol-lowering diet with either omega-3 fatty acids, soya proteins, plant sterols or plant stanols. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Inborn Errors of Metabolism Trials Register.Most recent search of the Group's Inborn Errors of Metabolism Trials Register: 09 October 2009.We also searched PubMed till 01 June 2008. SELECTION CRITERIA: Randomised controlled trials, both published and unpublished, where a cholesterol-lowering diet in children and adults with familial hypercholesterolaemia has been compared to other forms of dietary treatment or to no dietary intervention were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the trial eligibility and methodological quality and one extracted the data, with independent verification of data extraction by a colleague. MAIN RESULTS: In the present update, four new trials have been added making eleven trials with a total of 331 participants eligible for inclusion. Only short-term outcomes could be assessed due to the short duration of follow up in the included studies. None of the primary outcomes, (incidence of ischaemic heart disease, number of deaths and age at death) were evaluated in any of the included studies. No significant difference was noted for the majority of secondary outcomes for any of the planned comparisons. However, a significant difference was found only for the following comparison and outcome: total cholesterol levels for the comparison between plant sterols and cholesterol-lowering diet, mean difference 0.70 (95% confidence interval 0.19 to 1.21). AUTHORS' CONCLUSIONS: No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, due to the lack of adequate data. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein to a cholesterol-lowering diet.

18F-fluorodeoxyglucose positron emission tomography-based evaluation of systemic and vascular inflammation and assessment of the effect of systemic treatment on inflammation in patients with moderate-to-severe psoriasis: A randomized placebo-controlled pilot study.

BACKGROUND: Psoriasis is a systemic inflammatory disorder associated with an increased risk of cardiovascular disease. OBJECTIVE: To evaluate the utility of [[18]F]-fluorodeoxyglucose positron emission tomography/computed tomography in identifying vascular and systemic inflammation in psoriasis patients with moderate-to-severe disease and to analyze its usefulness in assessing the effect of systemic treatment. METHODS: This was a randomized, double-blind pilot study conducted in a tertiary care center. Baseline standardized uptake value score was estimated by18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with moderate-to-severe psoriasis and compared with historical controls. Patients were then randomized using computer-generated randomization list into methotrexate or placebo (with or without pioglitazone) groups.18F-fluorodeoxyglucose positron emission tomography/computed tomography was repeated at 12 weeks and composite standardized uptake value score determined. The correlation between Psoriasis Activity and Severity Index and SUVmax was assessed. RESULTS: A total of 16 patients were randomized to different treatment groups. Significant increase in mean SUVmax was observed in the ascending aorta in psoriasis patients as compared to historical controls (2.03 ± 0.53 vs 1.51 ± 0.36, P < 0.03). There was no difference in composite standardized uptake value score after 12 weeks of treatment in any of the treatment groups (P = 0.82), although an improvement in Psoriasis Activity and Severity Index score in the methotrexate arm was observed. No correlation was found between mean SUVmax and Psoriasis Activity and Severity Index scores in various aortic segments (r = 0.3-0.7). LIMITATIONS: Small sample size, short follow-up, historical controls, exclusion of patients with comorbid conditions and lack of surrogate markers of systemic inflammation. CONCLUSION: 18F-fluorodeoxyglucose positron emission tomography imaging showed higher vascular inflammation in ascending aorta of psoriasis patients as compared to historical controls. Systemic treatment with methotrexate and pioglitazone did not influence the vascular inflammation in the short term.

Pharmacoeconomic Analysis of Drugs Used in the Treatment of Pneumonia in Paediatric Population in a Tertiary Care Hospital in India-A Cost-of-Illness Study.

AIMS AND OBJECTIVES: The cost of antibiotic therapy for the treatment of pneumonia in the inpatient paediatric population can have a major impact on the healthcare expenditure. We planned to assess the direct and indirect costs of diagnosis and medical treatment of paediatric patients with community acquired pneumonia who are hospitalized in a tertiary care hospital in India. METHODS: 125 children with a diagnosis of pneumonia who were admitted to the inpatient department of a paediatric hospital receiving antibiotic treatment were observed. Data on clinical presentation and resources consumed were collected and the costs of pneumonia treatment were calculated. Descriptive statistics (mean ± standard deviation (SD)) were used to evaluate data regarding demographics, drugs prescribed and cost (direct and indirect cost). Multivariate regression analysis was used to find out predictors of direct and indirect cost. RESULTS: Among all pneumonia admissions, mild-to-moderate pneumonia constitutes 76.8%, and 23.2% children were admitted with severe pneumonia; 105 children out of 125 (84%) were suffering from associated disorders along with pneumonia. The majority of antibiotics prescribed belonged to beta lactams (52%) followed by aminoglycosides (19%), macrolides (13%) and peptides (11%). Parenteral routes of administration were used in a majority of patients as compared to oral. The average cost per patient in management of pneumonia was 12245 ± 593 INR ($187.34 ± 9.07).

Drug utilization study in medical emergency unit of a tertiary care hospital in north India.

Objective. To generate data on the drug utilization pattern and cost of drug treatment and to determine the rationality of prescriptions. Methods. A retrospective cross-sectional drug utilization study was conducted in the medical emergency unit of our hospital. Patient case records were reviewed to extract data on the pattern of drug use. Cost of drug treatment for the emergency visit was calculated by referring to the cost mentioned in Monthly Index of Medical Specialties and the rationality of prescriptions was evaluated using WHO core indicators of drug utilization. Results. 1100 case records were reviewed. Majority of patients received proton pump inhibitors followed by multivitamins. The median cost per prescription was 119.23$ (7.32$-7663.46$). Majority (49.9%) of drug cost was driven by antibiotics alone. An average of 4.9 drugs was prescribed per prescription. There were 14.89% encounters with antibiotics. 75.17% of the drugs were given as injectables and only 29.27% of the drugs were prescribed as generics. Conclusion. There is need to rationalize the drug therapy in terms of increasing prescribing of drugs by generic name and to avoid overuse of PPIs and multivitamins in emergency unit. Also the hospital pharmacy should be encouraged to procure more cost effective alternative antibiotics in future.

N-acetyl cysteine in clomiphene citrate resistant polycystic ovary syndrome: A review of reported outcomes.

Clomiphene citrate (CC) has been the gold-standard drug for ovulation induction in polycystic ovary syndrome (PCOS), but still CC resistance is seen in approximately 15-40% in women with PCOS. N-acetyl cysteine (NAC), a safe and cheap drug available in the market many years ago as mucolytic agent, was found to have a role in infertility management. Recently, some reports discussed the possible beneficial effects of NAC on ovulation. The biological properties of the NAC make this drug a potential candidate for its use in the infertility treatment, especially in the PCOS in inducing or augmenting ovulation. An updated electronic search was performed through PUBMED, MEDLINE, and COCHRANE and focused on peer-reviewed, full text, randomized controlled trials, and observational cohort or case-control studies for role of NAC in CC-resistant PCOS. Thorough search through all the clinical studies showed mixed results. Studies with positive results showed improvement in induction of ovulation as compared to negative studies showing contrary results. More randomized clinical trials are still needed to establish its definitive role in CC-resistant PCOS.

18F-fluorodeoxyglucose positron emission tomography-based evaluation of systemic and vascular inflammation and assessment of the effect of systemic treatment on inflammation in patients with moderate-to-severe psoriasis: A randomized placebo-controlled pilot study

Background: Psoriasis is a systemic inflammatory disorder associated with an increased risk of cardiovascular disease. Objective: To evaluate the utility of [[18]F]-fluorodeoxyglucose positron emission tomography/computed tomography in identifying vascular and systemic inflammation in psoriasis patients with moderate-to-severe disease and to analyze its usefulness in assessing the effect of systemic treatment. Methods: This was a randomized, double-blind pilot study conducted in a tertiary care center. Baseline standardized uptake value score was estimated by18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with moderate-to-severe psoriasis and compared with historical controls. Patients were then randomized using computer-generated randomization list into methotrexate or placebo (with or without pioglitazone) groups.18F-fluorodeoxyglucose positron emission tomography/computed tomography was repeated at 12 weeks and composite standardized uptake value score determined. The correlation between Psoriasis Activity and Severity Index and SUVmax was assessed. Results: A total of 16 patients were randomized to different treatment groups. Significant increase in mean SUVmax was observed in the ascending aorta in psoriasis patients as compared to historical controls (2.03 ± 0.53 vs 1.51 ± 0.36, P < 0.03). There was no difference in composite standardized uptake value score after 12 weeks of treatment in any of the treatment groups (P = 0.82), although an improvement in Psoriasis Activity and Severity Index score in the methotrexate arm was observed. No correlation was found between mean SUVmax and Psoriasis Activity and Severity Index scores in various aortic segments (r = 0.3–0.7). Limitations: Small sample size, short follow-up, historical controls, exclusion of patients with comorbid conditions and lack of surrogate markers of systemic inflammation. Conclusion: 18F-fluorodeoxyglucose positron emission tomography imaging showed higher vascular inflammation in ascending aorta of psoriasis patients as compared to historical controls. Systemic treatment with methotrexate and pioglitazone did not influence the vascular inflammation in the short term.

Pharmacotherapy of polycystic ovary syndrome--an update.

Polycystic ovary syndrome (PCOS) is a persisting challenge to clinical and basic research scientists as none of the presently available medications have been fully able to combat these consequences. The aim of the present review is to summarize the different lines of treatment available for the different symptomologies that women with PCOS presents. In this comprehensive review, search was made for various treatment options available for PCOS by using Cochrane library, Pubmed, Medline, in addition to the relevant printed medical journals and periodicals. The search results revealed that oral contraceptives containing oestrogen and progesterone regularize the menstruation, antiandrogens like spironolactone and drosperinone have proven to be effective in hirsutism and acne, clomiphene is the gold standard for ovulation induction, but multiple pregnancies and clomiphene failure add to its limitation. Hence, aromatase inhibitors like letrozole, low-dose gondotropins, and ovarian drilling procedure have shown to be beneficial effect in clomiphene-resistant cases. Insulin sensitizers such as metformin, thiazolidinediones, and d-chiro-inositol increase insulin sensitivity and improve ovulation rate. Recently, melatonin, N-acetyl cysteine, acarbose, and statins have shown positive results in different symptomologies of PCOS. The results show that PCOS treatment constitutes varied line of treatment depending upon the clinical features with which a woman is presenting. Still, unfortunately, none of the treatments are fully able to combat the PCOS.

Toxic Epidermal Necrolysis induced by rarely implicated drugs.

Toxic Epidermal Necrolysis (TEN) and Steven-Johnson Syndrome (SJS) are serious disorders commonly caused as idiosyncratic reactions to drugs, the most common ones being oxicams, anticonvulsants, allopurinol, and sulfonamides. We present a case of TEN in a patient who developed the lesions after ingesting multiple drugs including paracetamol, metoclopramide, antihistamines, and multivitamins. These drugs have rarely been implicated in this disorder. The suspected drugs in this case were paracetamol and metoclopramide. However, the role of other drugs could not be ruled out definitely. The patient was managed with antibiotics, corticosteroids, and parenteral fluids and recovered well.

Painful diabetic neuropathy: an update.

Diabetes, a silent killer, is a leading cause of neuropathy. Around 50% of diabetic patients develop peripheral neuropathy in 25 years. Painful diabetic neuropathy manifests as burning, excruciating, stabbing or intractable type of pain or presents with tingling or numbness. The pathophysiology of this condition is due to primarily metabolic and vascular factors. There is increase in sorbitol and fructose, glycated endproducts, reactive oxygen species and activation of protein kinase C in the diabetic state. All these factors lead to direct damage to the nerves. The first step in the management of painful diabetic neuropathy is a tight glycaemic control. Currently there is no drug which can halt or reverse the progression of the disease. Most of the therapies prevalent aim at providing symptomatic relief. Antidepressants like tricyclic antidepressants (TCAs) and selective norepinephrine reuptake inhibitors (SNRIs) have good efficacy in controlling the symptoms. Selective serotonin reuptake inhibitors have not shown the same consistent results. Anticonvulsants including pregabalin, gabapentin and lamotrigine have shown good results in the control of symptoms whereas same was not found with carbamazepine, oxcarbazepine and topiramate. Topical agents (capsaicin, topical nitrates and topical TCAs) and local anaesthetics have also been used with good results. Use of opioids and non steroidal anti-inflammatory drugs although common but is not preferable. The newer therapies under studies are NMDA antagonists, aldose reductase inhibitors, neurotropic factors, vascular endothelial growth factor, Gamma linolenic acid, protein kinase C beta inhibitors, immune therapy, hyperbaric oxygen and alpha lipoic acid.

Medical management of clomiphene-resistant polycystic ovarian syndrome: an update.

Clomiphene citrate is the traditional first-line treatment for chronic anovulation that characterizes polycystic ovary syndrome (PCOS). A gold standard therapy has always been Clomiphene Citrate (CC). However, 20%-25% of PCOS women fail to ovulate with incremental doses of CC. A good body of evidence suggest that alternatives for PCOS women with CC-resistant anovulation include insulin sensitizers like metformin and pioglitazone. Insulin sensitizers improves pregnancy outcome and ovulation rate by and acts by ameliorating insulin sensitivity and hyperandrogenemia. Metformin is preferred in obese women. Gonadotropins induce ovulation and maintain optimal follicle growth via controlled administration of follicle stimulation hormone. Two regimens are used which includes high and low dose regimen. Low dose regimen is preferred but is associated adverse effects like ovarian hyperstimulation syndrome (OHSS) and increased cost. Extending clomiphene therapy reduces cost and improves pregnancy outcome. Glucocorticoids are preferably used when serum Dehydroepiandrosterone levels are > 200µg/dL. Bromocriptine improves ovulation rate by decreasing prolactin levels. Human Chorionic Gonadotropin restores ovulation but its use is limited during intrauterine insemination. Tamoxifen acts in a similar way as CC but has lesser antiestrogenic effect on the endometrium, cervical mucus, and granulosa cells, hence an added advantage of monofollicular ovulation. Aromatase inhibitors block conversion androstenedione and testosterone to estrogen in ovary and improves ovulation rate. Added advantage includes lesser cost, simple to use, no danger of multiple pregnancies and convenient for patient. Combination of GnRH analogues and Gonadotropins are associated with increased risk of OHSS. D-chiro-inositol, N-Acetylcysteine, melatonin and acarbose are tried with little success.

Prescribing Pattern & Cost-Identification Analysis of Antimicrobial Use in Respiratory Tract Infections.

The objective of an observational study was to evaluate the drug prescribing pattern in the pediatric population in a tertiary care teaching hospital. The most common illness, which warranted admission to PICU, was bronchopneumonia (33.3%) followed by bronchiolitis (17.5%) and bronchial asthma (7.9%). Average no. of Antimicrobial Agents received per patient was 3.9. Parenteral drugs accounted for 86.1% of the total drugs prescribed. The most common AMAs prescribed were cephalosporins (26.1%), aminoglycosides (20.9%), beta-lactams (excluding cephalosporins) (17.4%) and fluoroquinolones (11.1%). Beta-lactams contributed to 44% of the total AMA cost followed by cephalosporins (31.8%) and miscellaneous AMAs (8.5%). The total number of preparation encounter per prescription was 9.7±4.8 per patient. The total number of single drug prescription was 88.4% and fixed drug combinations were 11.6%. Among the total drugs prescribed, 45.26% were generic and 54.73% constituted branded drugs. Overall 51% of the total drugs prescribed were from the WHO List of Essential Medicine 2010. There should be more emphasis on prescribing generic drugs and in case of similar efficacy the drug with lesser cost should be preferred.