Safety and Efficacy of Oral Transmucosal Fentanyl Citrate Compared to Morphine Sulphate Immediate Release Tablet in Management of Breakthrough Cancer Pain

Aim:

To compare the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) and oral morphine in Indian patients with breakthrough episodes of cancer pain.

Materials and Methods:

In this randomized, open label, active controlled, clinical study, total 186 patients who regularly experienced 1-4 episodes of breakthrough cancer pain (BTCP) daily, over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were randomized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days. Improvement in pain as determined by numerical rating scale (NRS) at 5, 15, 30, and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by >33% at 15 minutes were primary efficacy endpoints. Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient. Data of both treatment groups were analysed by appropriate statistical test using software, STATISTICA, version 11.

Results:

Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points (P < 0.0001). 56% of breakthrough pain episodes treated with OTFC showed a greater than 33% reduction in pain intensity from baseline at 15 minutes compared to 39% episodes treated with oral morphine (P < 0.0001). Patient''s and physician''s global assessment favoured OTFC than oral morphine (P < 0.0001). Requirement of rescue analgesia in both the study groups was similar (P > 0.05). Both study drugs were well tolerated.

Conclusions:

OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain.     

Oral Morphine Prescribing Practices in Severe Cancer Pain

Background:

Nearly one million cancer patients in India need oral morphine for pain relief. Despite doctors prescribing oral morphine in our center, many cancer patients with severe pain found to be not facilitated with adequate pain relief.

Aim:

This audit was conducted to look at the “oral morphine prescribing practices for severe cancer pain” at a tertiary care hospital.

Materials and Methods:

Twenty case files of patients, who were admitted with severe cancer pain, and receiving oral morphine were analyzed in pre- and posteducational session. Local standards were set to assess the adequacy of pain relief. Deficiency in achieving analgesia was found in preinterventional audit. A clinical audit was conducted before and after the educational session on oral morphine prescribing. The education for doctors and nurses focused on starting patients on morphine, titration, and administering rescue dose. Then local guidelines on oral morphine prescribing were circulated. And analysis of following factors were done following pre- and posteducational session: Pain intensity at the beginning of treatment, starting dose of morphine, increments in morphine dose, number of rescue doses given, and fall in pain intensity at the end of 1 week. The outcomes were compared with the standards.

Results:

Preintervention audit showed that only 50% of patients achieved adequate pain relief. Rescue dose was administered in only 20% of patients. While reaudit following the educational session showed that 80% of patients achieved adequate pain relief and 100% received rescue doses.

Conclusion:

Educational sessions have significant impact on improving oral morphine prescribing practice among doctors and nurses. It was found failing to administer regular as well as rescue doses resulted in inadequate pain relief in patients receiving oral morphine.     

Hypofractionated radiotherapy as local hemostatic agent in advanced cancer

Purpose:

Tumor bleeding continues to remain a challenge in an oncological setting, and radiotherapy has been studied as a local hemostatic agent. We studied the role of local radiotherapy in controlling bleeding at our center.

Materials and Methods:

We reviewed 25 treated cases (cancer urinary bladder: 12, lung cancer: 5, cervical cancer: 4, uterine cancer: 1, rectal cancer: 2, schwanoma: 1) at our center from March 2008 to December 2010. All patients had either an advanced or recurrent disease. Radiotherapy schedule was either 20 Gray in 5 fractions or 15 Gray in 5 fractions and was delivered with Cobalt 60.

Results and Conclusion:

Of 25 patients, 22 (88%) responded, and there was complete cessation of bleeding. Both 15 Gray and 20 Gray dose schedule had equal efficacy. Treatment was well tolerated without any intermission. Radiotherapy is a safe and effective option in controlling tumor bleeding.     

Oral health as a predictive factor for oral mucositis

OBJECTIVES:

Oral mucositis is a complication frequently associated with hematopoietic stem cell transplantation, decreasing a patient''s quality of life and increasing the occurrence of opportunistic infections. The purpose of this study was to determine the incidence and severity of oral mucositis and to assess the correlation of this disease with the oral health of an individual at the time of hematopoietic stem cell transplantation.

METHODS:

Before transplantation, patients'' oral health and inflammatory conditions were determined using the gingival index and the plaque index, which are based on gingival bleeding and the presence of dental plaque, respectively. Additionally, the dental health status was determined using the decayed, missing, and filled teeth index. The monitoring of oral mucositis was based on the World Health Organization grading system and was performed for five periods: from Day 0 to D+5, from D+6 to D+10, from D+11 to D+15, from D+16 to D+20, and from D+21 to D+30.

RESULTS:

A total of 97 patients (56% male and 44% female) who underwent hematopoietic stem cell transplantation at the Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo between January 2008 and July 2009 were prospectively examined. The incidence of ulcerative mucositis was highest from days +6 to +10 and from days +11 to +15 in the patients who underwent autologous and allogeneic hematopoietic stem cell transplantation, respectively.

CONCLUSION:

The data, including the dental plaque and periodontal status data, showed that these oral health factors were predictive of the incidence and severity of oral mucositis in a cohort of patients with similar conditioning regimens before hematopoietic stem cell transplantation.     

Effectiveness of Two High-dose-rate Intraluminal Brachytherapy Schedules for Symptom Palliation in Carcinoma Esophagus: A Tertiary Care Center Experience

Aim:

The aim was to analyze different radiation schedules with high-dose-rate (HDR) brachytherapy in patients with unresectable carcinoma esophagus in terms of dysphagia-free survival (DyFS), local control (LC), disease-free survival (DFS), and complications.

Materials and Methods:

Eighty-six patients were studied under three different radiation schedules: Schedule A – radiation 35 Gy/15# followed by HDR brachytherapy 6 Gy each in two sessions; schedule B – chemoradiation 35 Gy/15# with weekly injection cisplatin 30 mg/m² infusion and 5-fluorouracil 325 mg/m² bolus followed by HDR brachytherapy 6 Gy each in two sessions; and schedule C – same chemoradiation dose followed by HDR brachytherapy three sessions of 4.68 Gy each. The median follow-up was 12.1 months.

Results:

Treatment compliance was good. There were no significant differences in the incidence of acute toxicities across the three schedules. No grade III toxicities were noted. At 1 month, 27 patients had dysphagia improvement, which was not different across the three schedules. At 6 months, schedule C showed a trend toward better symptom control of dysphagia (dysphagia free=55%). The 2-year DyFS reached 49.5% in schedule C. Two-year LC rates were approximating 89% in both chemoradiation schedules versus 67.6% in schedule A. The 2-year DFS was also high in chemoradiation schedules. Major complications like ulceration and tracheoesophageal fistulas were more often seen with schedule B with a higher dose per fraction of the brachytherapy schedule.

Conclusion:

In unresectable carcinoma esophagus, radiation-only schedules are associated with lower LC and DFS rates. Concurrent chemoradiation followed by a brachytherapy boost is feasible in suitable patients with a good Karnofsky performance score and are associated with higher DyFS, LC, and DFS with acceptable toxicities. Still there is a need for the standardization of HDR brachytherapy schedules with chemoradiation protocols.     

Low-dose methotrexate therapy for intravenous immunoglobulin-resistant Kawasaki disease

Purpose

The aim of this study was to evaluate the efficacy of low-dose oral methotrexate (MTX) as a treatment for patients with Kawasaki disease (KD) which was resistant to intravenous immunoglobulin (IVIG).

Patients and Methods

The patients who had persistent or recrudescent fever after treatment with IVIG were subsequently treated with low-dose oral MTX [10 mg/body surface area (BSA)] once weekly.

Results

Seventeen patients developed persistent or recrudescent fever after treatment of KD with IVIG and were consequently given MTX. The proportion of children with coronary artery lesions (CALs) was 76%. The median value of maximum body temperatures decreased significantly within 24 hours of MTX therapy (38.6℃ vs. 37.0℃, p < 0.001). The median CRP (C-reactive protein) level was found to be significantly lower 1 week after administering the first dose of MTX (8.9 mg/dL vs. 1.2 mg/dL, p < 0.001). The median duration of fever before MTX treatment was shorter in CALs (-) group than in CALs (+) group (7 days vs. 10 days, p = 0.023). No adverse effects of MTX were observed.

Conclusion

MTX treatment for IVIG-resistant KD resulted in quick resolution of fever and rapid improvement of inflammation markers without causing any adverse effects. MTX therapy should further be assessed in a multicenter, placebo-blinded trial to evaluate whether it also improves coronary artery outcome.     

Effect of an Oral Hygienic Care Program for Stroke Patients in the Intensive Care Unit

Purpose

The effects of an oral hygienic care program (OHCP) have been reported in several diseases. However, no study exists investigating the influence of an OHCP on stroke patients or patients in the intensive care unit (ICU) has been reported, thus we sought to investigate the potential effect of an OHCP.

Materials and Methods

Fifty-six consecutive stroke patients who were admitted to the ICU were randomly assigned to two groups: the intervention (29 patients) and control groups (27 patients). The OHCP included tooth brushing with an inter-dental brush and tongue cleaner and cleaning with chlorhexidine was administered to patients by one dentist once per day during admission in the ICU (mean, 2.2 weeks). The plague index, gingival index, clinical attachment loss, and colonization degree of candida albicans were assessed.

Results

After OHCP, the plaque index, gingival index, and colonization degree of candida albicans in saliva showed a significant decrease in the intervention group compared to those of the control group (p<0.05). However, no significant difference was observed in clinical attachment loss and the colonization degree of candida albicans on the tongue (p>0.05).

Conclusion

Our OHCP was effective in improving the oral hygienic status and periodontal health of stroke patients during their stay in the ICU. Therefore, we recommend administration of the OHCP for stroke patients during their stay in the ICU.     

Positron emission tomography alone,positron emission tomography-computed tomography and computed tomography in diagnosing recurrent cervical carcinoma: a systematic review and meta-analysis

Introduction

The aim of the study was to assess systematically the accuracies of positron emission tomography (PET), PET/computed tomography (CT), and CT in diagnosing recurrent cervical cancer.

Material and methods

We searched for articles published from January 1980 to June 2013 using the following inclusion criteria: articles were reported in English; the use of PET, interpreted with or without the use of CT; use of CT to detect recurrent cervical cancer; and histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months. We extracted data to calculate sensitivity, specificity, summary receiver operating characteristic curves, and the area under the receiver operating characteristic curve (AUC) as well as test for heterogeneity.

Results

In 23 included studies, PET had the highest pooled specificity at 92% (95% CI: 90–94), whereas PET/CT had the highest pooled sensitivity at 94% (95% CI: 90–97). The area under the curve (AUC) of PET alone, PET/CT, and CT were 0.9594, 0.9508, and 0.9363, respectively. Results of the pairwise comparison between each modality show that the specificity of PET was higher than that of PET/CT (p < 0.05). The difference in the pooled sensitivities and AUC of PET alone and PET/CT showed no statistical significance. No evidence of publication bias was found. However, evidence of heterogeneity was observed.

Conclusions

The PET/CT may be a useful supplement to current surveillance techniques, particularly for patients with negative CT imaging. However, in terms of diagnostic accuracy, interpreted CT images may have limited additional value to PET in detecting recurrent cervical cancer.     

Anterior Cervical Discectomy and Fusion Alters Whole-Spine Sagittal Alignment

Purpose

Anterior cervical discectomy and fusion (ACDF) has become a common spine procedure, however, there have been no previous studies on whole spine alignment changes after cervical fusion. Our purpose in this study was to determine whole spine sagittal alignment and pelvic alignment changes after ACDF.

Materials and Methods

Forty-eight patients who had undergone ACDF from January 2011 to December 2012 were enrolled in this study. Cervical lordosis, thoracic kyphosis, lumbar lordosis, sagittal vertical axis (SVA), and pelvic parameters were measured preoperatively and at 1, 3, 6, and 12 months postoperatively. Clinical outcomes were assessed using Visual Analog Scale (VAS) scores and Neck Disability Index (NDI) values.

Results

Forty-eight patients were grouped according to operative method (cage only, cage & plate), operative level (upper level: C3/4 & C4/5; lower level: C5/6 & C6/7), and cervical lordosis (high lordosis, low lordosis). All patients experienced significant improvements in VAS scores and NDI values after surgery. Among the radiologic parameters, pelvic tilt increased and sacral slope decreased at 12 months postoperatively. Only the high cervical lordosis group showed significantly-decreased cervical lordosis and a shortened SVA postoperatively. Correlation tests revealed that cervical lordosis was significantly correlated with SVA and that SVA was significantly correlated with pelvic tilt and sacral slope.

Conclusion

ACDF affects whole spine sagittal alignment, especially in patients with high cervical lordosis. In these patients, alteration of cervical lordosis to a normal angle shortened the SVA and resulted in reciprocal changes in pelvic tilt and sacral slope.     

Cyclophosphamide in pulmonary alveolar hemorrhage due to leptospirosis

Background and Aims:

Severe pulmonary involvement in leptospirosis carries high mortality rates. It is the most common cause of death due to leptospirosis in many parts of India and the world. Exacerbated immune response of the host plays an important role in its pathogenesis. Hence, immunosuppressive drugs could be useful in its treatment. Glucocorticosteroids have been found to be useful in several studies. Cyclophosphamide, an immunosuppressive agent, has been found to be useful in a majority of pulmonary alveolar hemorrhages due to non leptospiral causes. This study was carried out to study the effects of cyclophosphamide in patients with leptospiral pulmonary alveolar hemorrhage.

Method:

A total of 65 patients with confirmed leptospirosis with severe pulmonary involvement admitted to a tertiary care center in south Gujarat were included in the study. All of the patients were treated with injection crystalline penicillin, methyl prednisolone pulse therapy, and non invasive mechanical ventilation. A total of 33 patients were given parenteral cyclophosphamide 60 mg/kg body weight stat on diagnosis. Their outcomes were compared with the remaining 32 patients who had not been given this drug. Survival was considered the main outcome indicator.

Results:

Out of the 33 patients treated with cyclophosphamide, 22 (66.7%) survived, while in the control group out of 32 patients, three (9.4%) survived. On statistical analysis, the odds ratio was 19.33 (4.22–102.13) and the P-value was <0.001. Leucopenia (78.78%) and alopecia (18.75%) were the main side effects noted. No mortality was noted due to these side effects.

Conclusion:

Cyclophosphamide improves survival in cases of severe pulmonary alveolar hemorrhage due to leptospirosis. Statistically, the improvement is highly significant.     

Arg389Gly β1-adrenergic receptor polymorphism and susceptibility to syncope during tilt test

Introduction

Numerous hormones, neurotransmitters, and other stimuli exert their biological effect on cellular functioning through heptahelical receptors coupled to G proteins (GPCR – G protein-coupled receptors). Adrenergic receptors that belong to this superfamily of receptors are components of the sympathetic nervous system. They play a pivotal role in blood pressure regulation and myocardial contractility. Alterations of the adrenergic receptor pathway have been suggested to be involved in the pathophysiology of vasovagal syncope (VVS). The aim of the present study was to evaluate the distribution of Arg389Gly polymorphism within the ADRB1 gene among patients with recurrent syncope.

Material and methods

Arg389Gly single nucleotide polymorphism was analyzed in 205 patients with recurrent syncope. Ninety-five patients (46%) had a positive head-up tilt test (HUT) result. The control group comprised 143 non-fainting subjects. Genotyping was performed by restriction fragment length polymorphism (RFLP) with BstNI enzyme.

Results

Both analyzed groups had similar distribution of the 389Gly allele. Sixty percent of polymorphic 389Gly carriers belong to the group of syncopal patients, while 40% belong to the control group of healthy subjects.

Conclusions

An association between syncopal incidence and Arg389Gly polymorphism within the ADRB1 gene was not found. The analyzed polymorphism affecting sympathetic activity does not influence vasovagal syncope in Polish patients.     

Selective Neck Dissection for Clinically Node-Positive Oral Cavity Squamous Cell Carcinoma

Purpose

The treatment of a clinically node-positive (cN+) neck is important in the management of oral cavity squamous cell carcinoma (OSCC). However, the extent of neck dissection (ND) remains controversial. The purpose of our study was to evaluate whether level IV or V can be excluded in therapeutic ND for cN+ OSCC patients.

Materials and Methods

We performed a retrospective chart review of 92 patients who underwent a comprehensive or selective ND as a therapeutic treatment of cN+ OSCC from January 1993 to February 2009.

Results

The incidence rate of metastasis to level IV or V was 22% (16 of 72) on the ipsilateral neck. Of 67 cases without clinically suspicious nodes at level IV or V, 11 cases (16%, 11 of 67) had pathologically proven lymphatic metastasis to level IV or V. Only a nodal staging above N2b was significantly relevant with the higher rate of level IV or V lymph node metastasis (p=0.025). In this series, selective ND, combined with proper adjuvant therapy, achieved regional control and survival rates comparable to comprehensive ND in patients under the N stage of cN2a OSCC.

Conclusion

In conclusion, level IV and V patients can avoid recurrence under cN2a OSCC.     

Relationship between mean platelet volume and recurrent miscarriage: a preliminary study

Introduction

The aim of the study was to examine the relationship between mean platelet volume (MPV) and recurrent miscarriage in order to illuminate the etiopathogenesis of recurrent miscarriage.

Material and methods

We retrospectively investigated the data of 120 patients with unexplained recurrent miscarriage (group 1), and compared them with the data of 120 match-paired patients in the control group (group 2). The definition of recurrent miscarriage was accepted as two or more failed clinical pregnancies which were documented by ultrasonography or histopathologic examination. All patients in the recurrent miscarriage group were evaluated with diagnostic tests for the etiology of recurrent miscarriage. Total blood count parameters, including hemoglobin, mean corpuscular volume, red cell distribution width, white blood cells, platelets, and mean platelet volume, were compared.

Results

The average patient age at the time of examination was 29.07 ±2.81 years in group I and 28.53 ±3.5 years in group II (p > 0.05). Mean body mass index (BMI) was similar between group 1 and group 2, 22.54 ±3.17 and 22.99 ±2.38, respectively (p > 0.05). Mean hemoglobin, mean corpuscular volume, red cell distribution width, and white blood cell and platelet levels were similar in both groups (p > 0.05). Mean platelet volume levels were significantly higher in group I (9.45 ±1.09 fl) than in group II (7.63 ±0.52 fl) (p = 0.001).

Conclusions

Higher MPV values in the study group suggest and support the importance of thromboembolic events in the etiology of recurrent miscarriage.     

Combined bipolar radiofrequency surgery of the tongue base and uvulopalatopharyngoplasty for obstructive sleep apnea

Introduction

The aim of the study was to investigate the effectiveness of combined bipolar radiofrequency surgery of the tongue base (RFBT) and uvulopalatopharyngoplasty (UPPP) in a single session for obstructive sleep apnea and whether this combination is safe and well tolerated.

Material and methods

Seventy-nine patients with obstructive sleep apnea and both palatal and retroglossal obstruction underwent UPPP with bipolar RFBT. The control group consisted of 35 patients treated by UPPP alone.

Results

The apnea-hypopnea index significantly decreased from 28.7 to 14.1. The oxygen desaturation index decreased from 15.1 to 10.3. Mean oxygen saturation was unchanged. Subjectively, the Epworth Sleepiness Scale was significantly improved from 10.6 to 7.3, and the snoring level decreased from 8.4 to 6.0. The overall treatment success rate increased from 41.9% for UPPP alone to 51.7% for UPPP + RFBT. No serious adverse events occurred. Two patients had postoperative bleeding from the tonsillar bed after UPPP. Four patients had ulceration of the base of the tongue after RFBT with spontaneous cure. One patient had a taste change in half of the tongue that resolved within two months.

Conclusions

Combined bipolar RFBT and UPPP in a single session is well tolerated and safe surgery in the treatment of obstructive sleep apnea. It is effective in reducing respiratory parameters and subjective symptoms of obstructive sleep apnea. Further advantages are a single session, simple feasibility, bipolar technique and short time of the procedure.     

The Role of Gefitinib in Patients with Non-small-cell Lung Cancer in India

Background:

Gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor, represents a new treatment option for patients with advanced non-small-cell lung cancer (NSCLC). We analyzed the data of patients who received Gefitinib for NSCLC in a tertiary care center in South India.

Materials and Methods:

Sixty-three patients with advanced NSCLC who had received Gefitinib either after failure of conventional chemotherapy or were previously not treated as they were unfit or unwilling for conventional treatment were included in the analysis.

Results:

The median follow-up for the cohort was 311 days (range 11-1544 days). Median time to progression was 161 (range 9-883) days. Complete and partial remission was seen in 1 (2%) and 6 (9%) patients, respectively, with overall response rate of 11%. Twenty-four (38%) patients had stable disease. Gefitinib was well tolerated with no significant side effects.

Conclusion:

Gefitinib shows anti-tumor activity in pretreated or previously untreated patients with advanced NSCLC. It has a favorable toxicity profile and is well tolerated. Gefitinib should be considered as a viable therapy in patients with NSCLC.     

Zero prevalence of parasites associated with oral lesions of HIV infected and AIDS patients in South Western Uganda

Background

Despite paucity of information regarding oral lesions with parasitic etiology, parasitic diseases continue to be problematic among impoverished and immunocompromised individuals in developing countries.

Objective

To determine the prevalence of parasites in the oral lesions of Ugandan HIV infected and AIDS patients, in South Western Uganda.

Methods

Adult HIV/AIDS positive patients attending The AIDS Support Organization Clinics in South Western Uganda with oral lesions were recruited for this study. Standard parasitological methods (direct microscopy, saline and iodine wet preparations, Giemsa-Romanosky staining of smears and culture) were adopted in analysis of randomly collected six hundred and five samples (469 from females; 136 from males) for parasites.

Results

No ova, cyst, trophoziotes, lava or segment of parasites were seen in the oral lesions identified among the studied population.

Conclusion

Parasites were absent and therefore may not be implicated as etiologic microbial agents of observed oral lesions associated with HIV infected and AIDS patients living in South Western Uganda     

Propofol versus flunitrazepam for inducing and maintaining sleep in postoperative ICU patients

Context:

Sleep deprivation is a common problem on intensive care units (ICUs) influencing not only cognition, but also cellular functions. An appropriate sleep-wake cycle should therefore be maintained to improve patients’ outcome. Multiple disruptive factors on ICUs necessitate the administration of sedating and sleep-promoting drugs for patients who are not analgo-sedated.

Aims:

The objective of the present study was to evaluate sleep quantity and sleep quality in ICU patients receiving either propofol or flunitrazepam.

Settings and Design:

Monocentric, randomized, double-blinded trial.

Materials and Methods:

A total of 66 ICU patients were enrolled in the study (flunitrazepam n = 32, propofol n = 34). Propofol was injected continuously (2 mg/kg/h), flunitrazepam as a bolus dose (0.015 mg/kg). Differences between groups were evaluated using a standardized sleep diary and the bispectral index (BIS).

Statistical Analysis Used:

Group comparisons were performed by Mann-Whitney U-Test. P < 0.05 was considered to be statistically significant.

Results:

Sleep quality and the frequency of awakenings were significantly better in the propofol group (Pg). In the same group lower BIS values were recorded (median BIS propofol 74.05, flunitrazepam 78.7 [P = 0.016]). BIS values had to be classified predominantly to slow-wave sleep under propofol and light sleep after administration of flunitrazepam. Sleep quality improved in the Pg with decreasing frequency of awakenings and in the flunitrazepam group with increasing sleep duration.

Conclusions:

Continuous low-dose injection of propofol for promoting and maintaining night sleep in ICU patients who are not analgo-sedated was superior to flunitrazepam regarding sleep quality and sleep structure.