Benzodiazepines Reduce Blood Pressure in Short Term: A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Benzodiazepines, due to their anxiolytic properties, are prescribed to reduce anxiety and insomnia. They might have hypotensive effect via potentiation of the inhibitory effect of gamma-amino butyric acid (GABA) in the central nervous system and vasodilatory properties. However, studies comparing the effect of benzodiazepines in lowering blood pressure (BP) are equivocal. This systematic review and meta-analysis was planned to assess the efficacy of benzodiazepines in reducing blood pressure in short term among hypertensive patients. RECENT FINDINGS: Various trials and retrospective analysis conducted previously have reported that benzodiazepines cause short- as well as long-term BP reduction in patients with increased anxiety with hypertension. On the other hand, several studies investigating the efficacy of benzodiazepines in patients with hypertension have reported inconclusive results. The primary question about the effect of benzodiazepines in lowering BP remains unanswered. In this meta-analysis of seven studies, benzodiazepines were found comparable to standard drugs in reducing systolic and diastolic BP in patients having hypertension. Although, the mean difference in systolic BP with benzodiazepines and placebo was statistically not significant, the difference can be considered as clinically meaningful. The current review offers preliminary evidence that benzodiazepines may have antihypertensive properties and may be used as add-on antihypertensive in a subset of patients in short term. The existing data are encouraging, but more clinical trials and mechanistic research are required to ascertain the long-term benefits.

Intranasal midazolam versus intravenous/rectal benzodiazepines for acute seizure control in children: A systematic review and meta-analysis.

BACKGROUND: Acute seizure activity might cause complications including bodily harm, progression to status epilepticus, and poor quality of life in children. The introduction of a venous line may be difficult in children with seizures which would delay the initiation of treatment. Rectal drug administration can be socially awkward for patients and providers. Intranasal (IN) midazolam offers a valuable substitute that is easier and faster to administer. OBJECTIVE: To assess the efficacy, safety, and acceptability of intranasal midazolam in children with acute seizure when compared to conventional IV or rectal benzodiazepine (BDZ). METHODS: PubMed, google scholar, websites clinicaltrials.gov and the WHO-international clinical trials registry platform, were searched. Randomized controlled/prospective randomized trials comparing IN midazolam against IV/rectal BDZ in the treatment of acute seizures in pediatric patients were included in the meta-analysis. RESULTS: Data of 10 studies were quantitatively analyzed. Intranasal midazolam (n = 169) when compared to IV/rectal BDZ (n = 161) has a shorter interval between hospital arrival and seizure cessation {(mean difference = -3.51; 95% CI [-6.84, -0.18]) P = 0.04}. Regarding time to seizure cessation after midazolam (n = 326) or BDZ (n = 322) administration, there is no significant difference between the two groups {(mean difference = -0.03; 95% CI [-1.30, 1.25]), P = 0.97} and both are equally effective for controlling acute seizures (odds ratio = 1.06; 95% CI [0.43, 2.63]; n = 737). CONCLUSION: In children with acute seizures, IN midazolam is equally effective in aborting seizure and decreases the total time from hospital arrival and cessation of seizures, eventually leading to faster cessation of seizure as compared to IV/rectal BDZ.

Effect of inhaled corticosteroids on serum periostin levels in adult patients with mild-moderate asthma.

Background: Periostin is an extracellular matrix protein, and its expression is upregulated in airway epithelial cells in patients with bronchial asthma. Periostin may be a key molecule linked to type 2 T-helper cell inflammation. Inhaled corticosteroids (ICS) may suppress periostin-induced asthmatic inflammation. This study estimated the serum periostin levels in patients with asthma and evaluated the effect of ICS on the levels of periostin, peak expiratory flow rate (PEFR), and quality of life (QOL). Methods: The study design was prospective, open label, and observational. Forty adults with mild-to-moderate bronchial asthma started on ICS and matched healthy controls were enrolled. The patients were evaluated for their serum periostin, PEFR, and QOL by using asthma QOL questionnaire scores at baseline and after 4 weeks. Results: The mean ± standard deviation (SD) serum periostin concentration in patients with asthma was 90.36 ± 19.81 ng/mL, which was significantly higher (p < 0.01) compared with healthy controls (31.88 ± 8.71 ng/mL). ICS treatment for 4 weeks reduced the mean ± SD serum periostin levels to 58.78 ± 14.53 ng/mL. The mean ± SD PEFR increased significantly, from 225.25 ± 60.79 L/min to 292.5 ± 59.18 L/min (p < 0.01), after 4 weeks. Similarly, the mean ± SD when using asthma QOL questionnaire scores significantly increased, from 40.7 ± 7.84 at baseline to 59.33 ± 11.0 on day 28 after ICS therapy (p < 0.01). Conclusion: The serum periostin level, a marker of allergic inflammation and remodeling, increased in bronchial asthma and was reduced with ICS therapy. ICS improved QOL scores and PEFR in patients with asthma.

Response to inhaled corticosteroids on serum CD28, quality of life, and peak expiratory flow rate in bronchial asthma.

BACKGROUND: CD28 is a 44 kDa glycoprotein that is important in initiating T-cell responses and that results in increased T-cell proliferation and interleukin-2 production. This study estimated the serum CD28 levels in patients with asthma and evaluated the effect of inhaled corticosteroids (ICS) on the levels of CD28, the peak expiratory flow rate (PEFR), and quality of life (QOL). METHODS: This prospective, open-label, observational study enrolled 40 adult patients with asthma of mild-to-moderate severity who were started on ICS and 40 healthy controls. Patients with bronchial asthma were evaluated for their serum CD28 level and QOL by using Mini Asthma Quality of Life Questionnaire scores, severity of symptoms, and PEFR at baseline and after 4 weeks. RESULTS: The mean (standard deviation [SD]) serum CD28 concentration in patients with asthma was 107 ± 4.98 ng/mL, which was significantly elevated (p < 0.01) compared with the healthy individuals (37.67 ± 18.28 ng/mL). ICS treatment for 4 weeks reduced the mean (SD) serum CD28 levels to 40.9 ± 2.82 ng/mL. PEFR increased significantly, from 190.75 ± 10.55 to 263 ± 10.69 L/min (p < 0.01) after 4 weeks. Similarly, the mean (SD) Mini Asthma Quality of Life Questionnaire scores significantly increased, from 36.90 ± 10.31 on day 0 to 70.63 ± 11.56 on day 28 after ICS therapy (p < 0.01). A negative correlation between the elevations of serum CD28 levels was seen with QOL. CONCLUSION: The serum CD28 concentration, a marker of inflammation, is increased in bronchial asthma and reduced by ICS therapy. ICS also improved QOL scores and objective clinical outcomes in patients with asthma.

Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression.

BACKGROUND: This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) levels in patients of major-depressive disorder (MDD) with severe depression. METHODS: Patients (aged 18-60) with MDD diagnosed by DSM-IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score ≥25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-α levels. RESULTS: HAM-D score at the start of treatment was 30.1 ± 1.92, which significantly (p < 0.05) reduced to 13.47 ± 1.77 at 12 weeks of treatment. In responders, mean serum BDNF levels at the start of treatment were 2.32 ± 0.3 ng/ml, which significantly (p < 0.05) increased to 2.79 ± 0.33 ng/ml at 12 weeks of treatment and mean serum TNF-α levels at the start were 5.18 ± 0.67 pg/ml, which significantly decreased to 4.36 ± 0.72 pg/ml (p < 0.05) at 12 weeks of treatment. CONCLUSION: Our results suggest that mirtazapine is effective and well tolerated in severely depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-α levels.

Therapeutic response of 70% trichloroacetic acid CROSS in atrophic acne scars.

BACKGROUND: Acne scarring is a common sequela of acne for which no single treatment method is uniformly effective. The chemical reconstruction of skin scars (CROSS) therapy using high-concentration trichloroacetic acid (TCA) has shown promise as a cheap, safe, and effective modality of treatment in acne scars. OBJECTIVE: To assess the therapeutic response of 70% TCA CROSS on atrophic acne scars and to evaluate the adverse effects of this therapy. MATERIALS AND METHODS: Fifty-three patients with postacne atrophic scars were treated with 70% of TCA focal application every 2 weeks by the CROSS technique and results evaluated on 3 parameters: physician assessment, patient assessment, and satisfaction level of patients, after a follow-up of 3 months. RESULTS: Good or excellent improvement (>50%) was seen in 66% of patients on physician and patient assessments. The patients were either very satisfied or satisfied in 81.1% of cases. Patients with predominantly boxcar scars and higher pretreatment scar severity were associated with better treatment outcomes. Age, sex, duration of scars, or type of skin did not significantly influence the treatment outcome and adverse effects. CONCLUSION: The study showed that 70% of TCA is a safe and effective treatment option in all types of atrophic acne scars, especially in severe boxcar scars.

Effect of systemic corticosteroids on serum apoptotic markers and quality of life in patients with asthma.

Despite corticosteroids being the first line drug treatment for asthma symptom control, the mechanisms of action of corticosteroids in asthma are still poorly understood. The current study aimed to evaluate the effect of systemic corticosteroids on serum level of apoptotic markers Survivin (for inflammatory cells) and M30 apoptosense (for bronchial epithelial cells) in patients of acute exacerbation of bronchial asthma. The study involved 60 patients with acute exacerbation of bronchial asthma who were prescribed systemic corticosteroids. Patients were evaluated for their serum levels of apoptotic markers (Survivin and M30 apoptosense) and their quality of life (QOL), before and after treatment with oral prednisolone. Paired t-test was used to compare the change in the serum values. The mean baseline serum Survivin and M30 apoptosense levels were 224.10 ± 42.76 and 123.00 ± 18.79 U/L, respectively, which decreased significantly (p < 0.05) to 111.20 ± 32.26 and 29.67 ± 7.53 U/L after seven days of oral prednisolone treatment. Systemic corticosteroids also significantly improved QOL scores and peak expiratory flow rate % (PEFR%) in the asthma patients. This improvement was seen irrespective of the initial severity score. Results from the study suggest that systemic corticosteroids administration decreases the survival of inflammatory cells and increases that of bronchial epithelial cells in patients with acute exacerbation of bronchial asthma. The study has been registered with Clinical Trials Registry-India. Registry database number CTRI/2014/08/00483.

Correction: Self-reported Morisky Eight-item Medication Adherence Scale for Statins Concords with the Pill Count Method and Correlates with Serum Lipid Profile Parameters and Serum HMGCoA Reductase Levels.

[This corrects the article DOI: 10.7759/cureus.6542.].

Effect of milnacipran on brain­derived neurotrophic factor and oxidative stress biomarkers in patients of major depressive disorder.

Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) suggest important role of neurotrophic factors and oxidative stress. This study assessed the effect of milnacipran (a dual serotonin­noradrenaline reuptake inhibitor) on brain­derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., malondialdehyde (MDA), glutathione­s­ transferase (GST) and glutathione reductase (GR) in patients of MDD. Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM­IV criteria, with Hamilton Depression Rating scale (HAM­D) score ≥ 14 were included in the study. Patients were given milnacipran in the doses of 50­100 mg once daily. Patients were followed up for 12 weeks. HAM­D score at the start of treatment was 17.8±1.7 which significantly reduced to 8.9±3.1 at 12 weeks of treatment. In responders, the plasma BDNF levels increased significantly at 12 weeks post treatment. There was no significant change in the pre­ and post­treatment values of oxidative stress parameters (MDA, GST and GR) after 12 week treatment. Milnacipran is effective and well tolerated in MDD patients, and its therapeutic response is associated with an increase in plasma BDNF levels. However, milnacipran did not affect oxidative stress biomarkers.

A Clinico-Epidemiological Study of Cutaneous Leishmaniasis in a Non-Endemic Region of South Rajasthan.

INTRODUCTION: Cutaneous leishmaniasis (CL) is a vector-borne protozoal infection of the skin with variable clinical manifestations. In Rajasthan, western Thar desert is endemic for this disease. AIM: The present study was aimed to describe clinico-epidemiological features of cutaneous leishmaniasis cases from a non-endemic area of South Rajasthan. MATERIALS AND METHODS: A hospital-based prospective study was carried out during a period of 3 years (2017-2019). Data regarding clinical profile and treatment outcome were recorded in a predesigned proforma for analysis. Diagnosis of CL was made clinically and confirmed by demonstration of amastigotes in microscopic examination of Giemsa stained tissue smear of lesions. RESULTS: Out of 24 patients, 16 (67%) were females and 8 (33%) were males. The age ranged from 3 months to 68 years (median-25). Face (67%) and extremities (29%) were the common sites affected. The most common morphological form was crusted plaques (54%) followed by nodular lesions (38%). Slit skin smear for Leishmania donovani bodies was positive in all patients (100%). CONCLUSION: This study highlights a focus of CL in non-endemic areas of South Rajasthan. Of late leishmaniasis is breaking out of its classical boundaries and is increasingly being reported from new geographic locations with a possibility of a novel parasite variant. Therefore, a high clinical suspicion of CL should be kept in non-endemic area.

Bupropion monotherapy alters neurotrophic and inflammatory markers in patients of major depressive disorder.

BACKGROUND: Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) indicate the role of neurotrophic factors and inflammation. This study assessed the association between therapeutic response of bupropion and serum brain-derived neurotrophic factor (BDNF) and tumour necrosis factor-α (TNF-α) levels in patients with MDD. METHODS: Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM-5 criteria, with Hamilton Depression Rating scale (HAM-D) score ≥ 20 were included in the study. Patients were given bupropion sustained release (SR) in the doses of 150 mg once daily. All patients were followed up for 12 weeks. RESULTS: HAM-D score at the start of the treatment was 25.57 ± 1.85 which significantly reduced to 10.8 ± 4.24 at 12 weeks of treatment. The serum BDNF level increased significantly (p < 0.05) from 2.42 ± 0.19 ng/ml to 2.97 ± 0.10 ng/ml and the levels of serum TNF-α reduced significantly (p < 0.05) from 4.45 ± 0.95 pg/ml to 2.11 ± 0.84 pg/ml at 12 weeks of treatment, in responders to treatment. CONCLUSION: The results of our study suggest that bupropion SR monotherapy is effective and well tolerated in MDD patients with moderate to severe depression, and its therapeutic efficacy is accompanied by an increase in serum BDNF levels and a decrease in serum TNF-α levels.

Effect of metformin and insulin combination on monocyte chemoattractant protein-1 and cathepsin-D in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Monocyte chemoattractant protein-1 (MCP-1) and cathepsin-D are progressively raised in type 2 diabetes mellitus (T2DM) with both non proliferative and proliferative retinal disease. This study aimed to evaluate the effect of antidiabetic medications on MCP-1 and cathepsin-D. METHODS: 60 patients of T2DM without retinopathy and 60 of diabetic retinopathy were enrolled to receive metformin (500 mg-1000 mg) combined with either glimepiride (1 mg-2 mg) or insulin. The effect of antidiabetic medications on serum MCP-1 and cathepsin-D was assessed. RESULTS: Mean MCP-1 (pg/ml) and cathepsin-D (ng/ml) levels were significantly lower in patients of T2DM with and without retinopathy treated with metformin + insulin (468.52 ± 272.84 vs 234.30 ± 180.58; p < 0.01 and 460.15 ± 128.52 vs 517.33 ± 213.49; p = 0.214) as compared to patients treated with metformin + glimepiride (1434.02 ± 105.27 vs 1256.27 ± 76.76; p < 0.01 and 1689.36 ± 752.57 vs 919.69 ± 675.05; p = < 0.01). No significant correlation of MCP-1 and cathepsin-D with HbA1c, fasting and post prandial blood glucose were found. CONCLUSION: Patients treated with metformin and insulin combination had lower serum MCP-1 and cathepsin-D levels which suggests that this combination may be more effective in reducing the progression of diabetic retinopathy. (CTRI/2018/05/013601).

Self-reported Morisky Eight-item Medication Adherence Scale for Statins Concords with the Pill Count Method and Correlates with Serum Lipid Profile Parameters and Serum HMGCoA Reductase Levels.

Background It is imperative that non-compliance with statins be identified and addressed to maximize their clinical benefits. Patient self-reporting methods are convenient to apply in clinical practice but need to be validated. Objective We studied the concordance of a patient self-report method, Morisky eight-item medication adherence scale (MMAS)), with the pill count method in measuring adherence with statins and their correlation with extended lipid profile parameters and serum hydroxyl-methylglutaryl coenzyme A reductase (HMGCoA-R) enzyme levels. Methods MMAS and the pill count method were used to measure the adherence with statins in patients on statins for any duration. Patients were subjected to an estimation of extended lipid profile and serum HMGCoA-R levels at the end of three months follow-up. Results Out of a total of 200 patients included in the study, 117 patients had a low adherence (score less than 6 on MMAS) whereas 65 and 18 patients had medium (score 6 or 7) and high adherence (score of 8), respectively. The majority of patients who had low adherence to statins by MMAS were nonadherent by the pill count method yielding a concordance of 96.5%. Medium or high adherence to statins by the MMAS method had a concordance of 89.1% with the pill count method. The levels of total cholesterol, low-density lipoprotein-cholesterol, apolipoprotein B, and HMGCoA-R were negatively correlated with compliance measured by pill count and MMAS in a statistically significant way and with similar correlation coefficients. HMGCoA-R levels demonstrated a plateau phenomenon, with levels being 9-10 ng/ml when compliance with statin therapy was greater than 60% by pill count and greater than 6 on the Morisky scale. Conclusion In conclusion, MMAS and the pill count method showed concordance in measuring adherence to statins. These methods need to be explored further for their interchangeability as surrogates for biomarker levels.

A Randomized double Blind Controlled Study Comparing the Efficacy of Intralesional MMR Vaccine with Normal Saline in the Treatment of Cutaneous Warts.

BACKGROUND: Recently, with better understanding of the immunology of warts, immunotherapeutic approaches have emerged as an effective treatment option for the management of cutaneous warts. Intralesional immunotherapy with MMR vaccine is one such modality but there are still lack of enough placebo-controlled studies. AIM: To evaluate the efficacy of intralesional MMR in patients of extragenital warts in a double-blinded manner using normal saline as control. PATIENTS AND METHODS: One hundred patients of extragenital cutaneous warts were randomly allocated into two groups, the interventional (MMR) group and control (normal saline) group. MMR vaccine was injected intralesionally in the patients belonging to interventional group, a similar volume of normal saline (NS) was injected in the control group. The outcome in terms of treatment response, adverse effects, and recurrences were evaluated and compared. RESULTS: Eighteen of thirty (60%) patients in the interventional group achieved complete response as against 7 (23.3%) in the control group (P = 0.01). Distant warts cleared in 69.5% patients in the interventional groupcompared to none in the control group. Adverse effects seen in both groups were injection site pain and mild erythema. A total of 57.1% patients showed recurrences in the control group compared to 16.6% in the interventional group. CONCLUSION: Intralesional MMR vaccine is an effective treatment option in patients with multiple extragenital warts. It is suggested that it should be used as first-line therapy for multiple warts and a second-line therapy for warts recalcitrant to standard therapies.

Diffuse Cutaneous Leishmaniasis in an Immunocompromised Patient Resembling Histoid Hansen's Disease.

Cutaneous leishmaniasis is caused by protozoan parasites of the genus Leishmania. Atypical presentation and widespread progression of the lesions may be seen in patients with HIV disease and diffuse cutaneous leishmaniasis and HIV co-infection is emerging as a serious new threat. We report a case of diffuse cutaneous leishmaniasis in a HIV- infected patient resembling Histoid Hansen.