Dosimetric comparison of O-ring versus conventional C-arm linear accelerator for volumetric modulated arc therapy (VMAT) of head and neck cancer and carcinoma cervix patients.

The objective of this study is dosimetric comparison between the O-ring Halcyon and C-arm Clinac iX linac for volumetric modulated arc therapy (VMAT) plans for head & neck (H&N) cancer and carcinoma cervix patients. Total 60 patients of H&N cancer and carcinoma cervix were enrolled prospectively from March 2021 to March 2023. VMAT plans with 6 MV photons for Halcyon and Clinac iX were generated and compared for each patient by dose volume histogram for planning target volume coverage and organ at risk (OAR) sparing. There were no differences in between both the linacs for PTV D2% and D98%, homogeneity index, conformity index, Dmax (maximum dose) and Dmean (mean dose) of OAR. Halcyon had significantly shorter treatment time compared to Clinac iX. Halcyon delivered higher integral dose and monitor units. O-ring Halcyon produces VMAT plans comparable to other C-arm linacs for H&N and carcinoma cervix patients.

Target volume coverage in clinically designed radiotherapy plan of post-mastectomy adjuvant radiotherapy of breast cancer patients in comparison with radiation therapy oncology group-based contoured plan: A dosimetric study.

Objective: Conventional field radiotherapy based on anatomical landmarks has been the traditional treatment for breast cancer. Having proven efficacy, it is still the current standard of treatment. The Radiation Therapy Oncology Group (RTOG) has published guidelines for contouring target volumes in postmastectomy patients. The impact of this guideline in the current clinical practice is less known; hence, we have analyzed dose-volume histograms (DVHs) for these plans and compared them with the proposed treatment plans to treat RTOG-defined targets. Subjects and Methods: RTOG consensus definitions were used to contour the target volumes in 20 previously treated postmastectomy patients. The prescription was 42.4 Gy in 16 fractions. DVHs were generated from clinically designed plans that had actually been delivered to each patient. For comparing dose to target volumes, new plans were generated with the goal of covering 95% of volume to 90% of prescribed dose. Results: In RTOG contoured Group, coverage improved for the supraclavicular (V90 = 83 vs. 94.9%, P < 0.05) and chest wall (V90 = 89.8 vs. 95.2%, P < 0.05). Axillary nodal coverage improved for Level-1(V90 = 80.35 vs. 96.40%, P < 0.05), Level-II (V90 = 85.93 vs. 97.09%, P < 0.05) and Level III (V90 = 86.67 vs. 98.6%, P < 0.05). The dose to the ipsilateral lung is increased (V20 = 23.87 vs. 28.73%, P < 0.05). Low dose to heart is increased in left-sided cases (V5 = 14.52 vs. 16.72%, P < 0.05) while same in right-sided cases. Conclusions: The study shows that radiotherapy using the RTOG consensus guidelines improves coverage to target volumes with a nonsignificant increase in normal organ dose compared to that based on anatomical landmarks.

Comparative Efficacy of Levosalbutamol and Racemic Salbutamol in the Treatment of Acute Exacerbation of Asthma.

Asthma is a major noncommunicable disease (NCD), affecting both children and adults, and is the most common chronic disease among children. It is common in all ages and the prevalence is increasing in most countries, especially among children as because of urbanization. Multiple therapeutic modalities are available for management of acute asthma. The commonly used formulation is Racemic Salbutamol which contains equal amounts of both R and S isomers. Levosalbutamol contains only R isomer. The aim of the study was to compare the efficacy of levosalbutamol and racemic salbutamol for the treatment of acute exacerbation of asthma in children (5 to 15 years). A randomized double blind clinical trial was conducted in the Department of Paediatrics, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh from October 2013 to March 2014. In this study randomization was done in two groups. Group A received nebulized levosalbutamol (LEV) and Group B received nebulized racemic salbutamol (RAC). The study parameters were respiratory rate (RR), heart rate (HR), oxygen saturation in room air (SpO2), PEFR, asthma score and serum K+ level. The results of treatment outcome were compared between two groups. After treatment the respiratory rate was 24.4±5.6 per minute versus 27.6±5.3 per minute (p<0.05); heart rate was 115.5±16.4 per minute versus 124.5±12.0 per minute (p<0.05); SpO2 was 97.2±1.8% vs 95.0±1.6% (p<0.05); PEFR was found 159.6±30.7L/min versus 143.8±27.1L/min (p<0.05) in the LEV and RAC group respectively. LEV is more effective than RAC in respect to significant improvement of asthma score. Regarding adverse events racemic salbutamol causes significant tachycardia. The study concluded that nebulized levosalbutamol is superior to racemic salbutamol in children in the treatment of acute exacerbation of asthma.

Effect of Eye Spray Phospholipid Concentration on the Tear Film and Ocular Comfort.

OBJECTIVES: To evaluate the effect of eye spray phospholipid concentration on symptoms and tear film stability. METHODS: High-concentration (Tears Again, Optima Pharma GmbH, Hallbergmoos, Germany) and low-concentration (Ocuvers, Innomedis AG, Germany) phospholipid eye sprays were sprayed onto the closed eyelids of 30 subjects (33.2±1.8 years; 20 women) in a multicentered, prospective, crossover study. Ocular comfort (visual analog scale) and noninvasive tear film stability (NIBUT) of each eye were evaluated before application (along with the Ocular Surface Disease Index), 10 min after application, and 30 min after application. RESULTS: Comfort (high concentration: 68.5±16.4 vs. low concentration: 70.7±14.5 phospholipid) and NIBUT (high concentration: 11.5±4.6 sec vs. low concentration: 11.2±6.0 sec phospholipid) were not different (P>0.3) between sprays before application, but comfort (by 12 points, P=0.001) and NIBUT (by 5 sec, P=0.016) were significantly better with a high-concentration phospholipid spray at both 10 min and 30 min time points than those with the low-concentration phospholipid spray. CONCLUSIONS: The liposomal eye spray with higher concentration of phospholipids significantly improved ocular comfort and tear film stability in contrast to the eye spray with lower concentration of phospholipids, hence practitioners need to choose an appropriate eye spray to maximize the patient benefit.

Pelvic bone anatomy vs implanted gold seed marker registration for image-guided intensity modulated radiotherapy for prostate carcinoma: Comparative analysis of inter-fraction motion and toxicities.

OBJECTIVES: We compared the prostate motion variability and toxicities between patients treated with gold marker registration based IG-IMRT (IG-IMRT-M) and bony landmark registration based IG-IMRT (IG-IMRT-B). METHODS: T1c-T3b (node negative), intermediate and high risk (non-metastatic) adenocarcinoma of prostate, age ≥18years, Karnofsky Performance Status of ≥70 were included in this retrospective study. The prostate motion variability, acute and late radiation toxicities between the two treatment arms (IG-IMRT-M versus IG-IMRT-B) were compared. RESULTS: Total of 35 patients (17 for IG-IMRT-M and 18 for IG-IMRT-B) were treated with a median radiotherapy dose of 76 Gray. The prostate variability observed with and without markers in millimeter was 4.1±2.3 vs 3.7±2.1 [Antero-Posterior (A-P); p=0.001], 2.3±1.5 vs 2.1±1.2 [Superior-Inferior (S-I); p=0.095] and 1.1±1.7 vs 0.4±1.4 [Left-Right (L-R); p=0.003]. There was higher acute toxicity in IG-IMRT-B arm compared to IG-IMRT-M arm in terms of grade ≥2 diarrhea [50% vs 11% OR=7.5 (1.3-42.7); p=0.02] and grade ≥2 proctitis [38% vs 5.8%, OR=10.1 (1.09-94.1); p=0.04]. At a median follow up of 36months, the late genitourinary toxicities grade ≥2 [27% vs 0%; p=0.04] were higher in the IG-IMRT-B arm compared to IG-IMRT-M arm. CONCLUSIONS: IG-IMRT-M detects higher prostate motion variability as compared to IG-IMRT-B, inferring a significant prostate motion inside fixed pelvic bony cavity. The addition of marker based image guidance results in higher precision of prostate localization and lesser acute and late toxicities.

Residual disease and HPV persistence after cryotherapy for cervical intraepithelial neoplasia grade 2/3 in HIV-positive women in Kenya.

OBJECTIVE: To assess residual cervical intraepithelial neoplasia (CIN) 2/3 disease and clearance of high-risk (hr) human papillomavirus (HPV) infections at 6 months after cryotherapy among HIV-positive women. DESIGN: Follow-up study. METHODS: 79 HIV-positive women received cryotherapy for CIN2/3 in Nairobi, Kenya, and underwent conventional cytology 6 months later. Biopsies were performed on high grade cytological lesions and hrHPV was assessed before (cervical cells and biopsy) and after cryotherapy (cells). RESULTS: At 6 months after cryotherapy CIN2/3 had been eliminated in 61 women (77.2%; 95% Confidence Interval, (CI): 66.4-85.9). 18 women (22.8%) had residual CIN2/3, and all these women had hrHPV at baseline. CD4 count and duration of combination antiretroviral therapy (cART) were not associated with residual CIN2/3. CIN3 instead of CIN2 was the only significant risk factor for residual disease (odds ratio, OR vs CIN2 = 4.3; 95% CI: 1.2-15.0) among hrHPV-positive women after adjustment for age and HPV16 infection. Persistence of hrHPV types previously detected in biopsies was found in 77.5% of women and was associated with residual CIN2/3 (OR = 8.1, 95% CI: 0.9-70). The sensitivity, specificity, and negative predictive value of hrHPV test in detecting residual CIN2/3 were 0.94, 0.36, and 0.96 respectively. CONCLUSIONS: Nearly one quarter of HIV-positive women had residual CIN2/3 disease at 6 months after cryotherapy, and the majority had persistent hrHPV. CD4 count and cART use were not associated with residual disease or hrHPV persistence. The value of hrHPV testing in the detection of residual CIN2/3 was hampered by a low specificity.

Comparison of HPV DNA testing in cervical exfoliated cells and tissue biopsies among HIV-positive women in Kenya.

HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4-5.7). PR diminished with the increase in lesion severity (PR in 58 women with high-grade squamous intraepithelial lesions (HSIL)/CIN2-3 = 1.1; 95% CI: 1.0-1.2). When HPV-positive, cells contained 2.0- to 4.6-fold more multiple infections than biopsies. Complete or partial agreement between cells and biopsies in the detection of individual HPV types was found in 91% of double HPV-positive pairs. The attribution of CIN2/3 to HPV16 and/or 18 would decrease from 37.6%, when the presence of these types in either cells or biopsies was counted, to 20.2% when it was based on the presence of HPV16 and/or 18 (and no other types) in biopsies. In conclusion, testing HPV on biopsies instead of cells results in decreased detection but not elimination of multiple infections in HIV-positive women. The proportion of CIN2/3 attributable to HPV16 and/or 18 among HIV-positive women, which already appeared to be lower than that in HIV-negative, would then further decrease. The meaning of HPV detection in cells and random biopsy from HIV-positive women with no cervical abnormalities remains unclear.

Cervical squamous intraepithelial lesions among HIV-positive women on antiretroviral therapy in Kenya.

BACKGROUND: The prevalence of cervical squamous intraepithelial lesions (SIL) among HIV-infected women on antiretroviral therapy in sub-Saharan Africa has not been well described. METHODS: HIV-infected women enrolled in an HIV treatment clinic in Nairobi, Kenya were offered free cervical screening with Papanicolaou (Pap) smear testing if they were 30 to 39 years of age and on antiretroviral therapy. Women with SIL were compared to those without SIL with univariate analyses and logistic regression. RESULTS: Of 595 eligible women, 267 accepted Pap testing and had available cytology results, of whom 258 (97%) were on a non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen. Median duration of antiretroviral therapy was 13 months [interquartile range (IQR), 8-19]. Abnormal cytology was found in 123 women (46%) with 70 women (26%) having low grade squamous intraepithelial lesions (LSIL), 22 (8%) high grade squamous intraepithelial lesions (HSIL), 30(11%) atypical squamous cells of unknown significance (ASCUS) and 1 (0.4%) atypical glandular cells (AGC). Women with SIL had lower median CD4 cell count (239 vs 287 cells/mm3; P=0.02), lower income (<70 USD per month: 57% vs 38%; P=0.01), and less regular condom use (24% vs 40%; P=0.02) compared to those with no SIL. Duration and type of antiretroviral regimen were not significantly associated with SIL. CONCLUSION: SIL is prevalent among women on antiretroviral therapy and is associated with immunosuppression, low income, and less frequent condom use. Cervical cancer screening and counseling on condom use should be routinely offered to HIV-infected women in antiretroviral treatment clinics in Africa.

An optimized commercially feasible milling technique for molecular encapsulation of meloxicam in ß-cyclodextrin.

BACKGROUND: The practical applicability of solid dispersions (SD) for improvement of oral bioavailability of poorly water-soluble drugs has still remained limited because of lack of feasibility for scale-up of manufacturing processes. The present research work deals with the preparation of SDs of meloxicam (MLX) with ß-cyclodextrin (ß-CD) by the ball-milling technique to overcome the scale-up issues. METHODS: Phase-solubility studies were conducted to analyze the influence of ß-CD on solubility of MLX. In vitro dissolution studies on various complexes as well as tablets prepared on pilot scale in an industrial set up were performed and compared with the marketed products. Physicochemical characterization of optimized complexes was done using various methods to study drug-ß-CD interaction. RESULTS: Solubility of pure MLX in water at 25°C was found to be only 9.4 µg/mL. The AL type of phase-solubility profile of MLX with ß-CD [stability constant (K(1:1)) = 22.056 M(-1) and Gibbs free energy (ΔF(o)) = -7.665 KJ/mole] confirmed the solubility enhancement capability of ß-CD. Milling time of 6 h was considered to be optimum and showed maximum enhancement of drug dissolution. The amorphous nature of the milled complex and mode of interaction of MLX with ß-CD was confirmed by differential scanning calorimetry (DSC), x-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectrophotometry ((1)HNMR). Tablets containing MLX-ß-CD (1:1.5 M) milled complexes showed the best release (T(90%) = 10.94 min) compared to the marketed products (T(90%) ≥ 450 min). Stability studies performed confirmed the integrity of the amorphous complex. CONCLUSION: Stable inclusion complexes of MLX-ß-CD with enhanced aqueous solubility and dissolution rate were prepared by a highly efficient and controlled large-scale milling technique.

Ferritin and Soluble Transferrin Receptors in Type 2 Diabetic and Non-diabetic Post-menopausal Women in Dhaka, Bangladesh.

This cross-sectional comparative study was aimed at investigating the iron status of a group of post-menopausal women with and without diabetes. Thirty-five post-menopausal women in each group were selected purposively from among patients attending the out-patient department of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), a specialist hospital, and two of its satellite clinics, all in Dhaka. Patients were enrolled based on their existing records. The subjects were matched on age, menstrual status and fasting status at blood draw. Ferritin, serum soluble transferrin receptors (sTfR) and fasting plasma glucose were measured by standard methods. Dietary information was collected by a specific food frequency questionnaire. No significant difference in plasma ferritin [62.02 ng/ml, (range: 4.68-288.89) vs 54.25 ng/ml (range: 4.58-137.17); p=0.28] was observed between the groups. But a higher level of plasma sTfR was found in diabetic women [(21.12 nmol/l (range: 7.91-39.79) vs 17.63 nmol/l (range: 10.30-110.00); p<0.01]. TFR-F index showed no difference between diabetic and control (p=0.25). Significantly a lower hemoglobin level [10.58±0.67 g/dl vs11.76±1.5 g/dl; p<0.01] was detected in diabetic women. Plasma sTfR (log) did not show any significant association with the dietary parameters and iron indices. No significant association between fasting glucose, ferritin and sTfR was seen except for haemoglobin (r=0.39, p=0.05). Total iron intake recorded was more than the requirement, and was significantly higher in control group [38.11mg/day (range: 19.83-105.63) vs 56.65 mg/day (range: 29.75-109.54); p<0.01)]. More than 97 % of total iron was of plant origin. No differences in heme iron [0.85 mg/day (range: 0.09-4.07) vs. 0.96 mg/day (range: 0.04-4.34), p= 0.17] and vitamin C intake was observed between the groups. Iron indices of non-diabetic women were within the normal range. A higher level of sTfR and a lower level of hemoglobin in diabetic cases is suggestive of iron deficiency anaemia rather than iron overload.

Ferritin and Soluble Transferrin Receptors in Type 2 Diabetic and Non-diabetic Post-menopausal Women in Dhaka, Bangladesh

This cross-sectional comparative study was aimed at investigating the iron status of a group of post-menopausal women with and without diabetes. Thirty-five post-menopausal women in each group were selected purposively from among patients attending the out-patient department of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), a specialist hospital, and two of its satellite clinics, all in Dhaka. Patients were enrolled based on their existing records. The subjects were matched on age, menstrual status and fasting status at blood draw. Ferritin, serum soluble transferrin receptors (sTfR) and fasting plasma glucose were measured by standard methods. Dietary information was collected by a specific food frequency questionnaire. No significant difference in plasma ferritin [62.02 ng/ml, (range:4.68-288.89) vs 54.25 ng/ml (range: 4.58-137.17); p=0.28] was observed between the groups. But a higher level of plasma sTfR was found in diabetic women [(21.12 nmol/l (range: 7.91-39.79) vs 17.63 nmol/l (range: 10.30-110.00); p<0.01]. TFR-F index showed no difference between diabetic and control (p=0.25). Significantly a lower hemoglobin level [10.58±0.67 g/dl vs11.76±1.5 g/dl; p<0.01] was detected in diabetic women. Plasma sTfR (log) did not show any significant association with the dietary parameters and iron indices. No significant association between fasting glucose, ferritin and sTfR was seen except for haemoglobin (r=0.39, p=0.05). Total iron intake recorded was more than the requirement, and was significantly higher in control group [38.11mg/day (range: 19.83-105.63) vs 56.65 mg/day (range: 29.75-109.54); p<0.01)]. More than 97 % of total iron was of plant origin. No differences in heme iron [0.85 mg/day (range:0.09-4.07) vs. 0.96 mg/day (range: 0.04-4.34), p= 0.17] and vitamin C intake was observed between the groups. Iron indices of non-diabetic women were within the normal range. A higher level of sTfR and a lower level of hemoglobin in diabetic cases is suggestive of iron deficiency anaemia rather than iron overload.