False negative rate of fine‐needle aspiration in thyroid nodules: impact of nodule size and ultrasound pattern

Abstract

Background

To retrospectively evaluate the false negative rate of ultrasound‐guided fine needle aspiration (FNA) according to the nodule size and ultrasound pattern.

Methods

We included 432 consecutive thyroid nodules from 384 patients who underwent ultrasound‐guided FNA with benign results (≥1 cm). The false negative rate in the nodules was assessed according to the nodule size and ultrasound pattern based on the Korean‐Thyroid Imaging Reporting and Data System (K‐TIRADS).

Results

The overall false negative rate was 3.2%. There was a trend toward an increasing false negative rate as the K‐TIRADS score increased (P < .001). In low or high suspicion nodules (K‐TIRADS 3 and 5), there was no significant difference in false negative rate according to the nodule size; however, among the intermediate suspicion nodules (K‐TIRADS 4), the false negative rate was higher in large nodules (≥3 cm, P = .039).

Conclusion

The impact of nodule size on the false negative rate differed according to the ultrasound pattern.

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Juvenile nasopharyngeal angiofibroma: A retrospective study of 27 cases in the ent Department of ipo‐Porto

Abstract

Juvenile nasopharyngeal angiofibroma (JNA) is a benign, rare and highly vascular tumour, occurring in adolescent males.

Clinical records of 27 patients who underwent surgical resection, performed between 1989 and 2017, were reviewed.

Three patients were submitted to paralatero‐nasal rhinotomy, 23 patients (85%), to the sublabial transnasomaxillary approach (Rouge Denker approach), complemented in 19 (70.0%) with transpalatine approach (Wilson technique). Endoscopic resection was performed only at one patient stage IB.

There were no cases of death, major significant complications or significant morbidity. Persistence rate was 18.5% and recurrence rate 14.8%.

Patients with tumour extension to infratemporal fossa and no massive cavernous sinus invasion may be treated effectively without previous embolization and facial scars, with sublabial transnasomaxillary approach (Rouge Denker approach), complemented with transpalatine approach (Wilson technique).

This article is protected by copyright. All rights reserved.

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Clinico-Pathological Correlation

Correlation between total serum bilirubin and clinico-laboratory parameters of babies admitted for neonatal jaundice in a resource-limited setting Uchenna Ekwochi, Chidiebere D.I Osuorah, Ikenna Kingsley Ndu International Journal of Clinicopathological Correlation 2018 2(2):21-26 Background: Neonatal jaundice (NNJ) is one of the most frequent reasons newborn babies in low- to middle-income countries visit the hospital during the neonatal period. If not promptly managed, it could lead to serious neurological sequela and mortality. The level and type of bilirubin in serum are an important determinant of the management option in NNJ. Unfortunately, this simple but fundamental investigation is not readily available in many hospitals in low- to middle-income countries, and where available, needs to be done serially, an expenditure most clients cannot afford. Methodology: This study enrolled 83 newborns admitted and managed for NNJ at the Enugu State University Teaching Hospital during an 18-month period. We report correlation between total serum bilirubin (TSB) and selected newborn clinical and laboratory parameters. Results: A total of 83 newborns were admitted for NNJ during the study. The mean TSB (mTSB) was 307 ± 145.2 μmol/L. Preterm infants (T = 0.462, P = 0.500), neonates with birth weight <2.5 kg (T = 0.219, P = 0.804), female neonate (T = 0.314, P = 0.578), and those that presented with skin level at the lower body region (T = 28.52, P = 0.001) had a higher mTSB at presentation to the special care baby unit. Similarly, mTSB at presentation was higher in neonates with PCV <40% (T = 0.005, P = 0.942), negative malaria parasite film (T = 0.01, P = 0.933), and those that were Glucose-6-Phosphate dehydrogenase deficient (T = 1.59, P = 0.221). Only skin level of jaundice at presentation was significantly correlated to the TSB (R = 0.818 P = 0.001) while gestational age (R = 0.096, P = 0.500), age at presentation (R = 0.197, P = 0.157), and birth weight (R = −0.107, P = 0.459) were not. Linear regression analysis showed that for every regional rise in skin level of jaundice (X), the TSB (Y) in μmol/L increases by a factor of 89.74 expressed in a regression equation as, Y = −10.66 + 89.74 X. Conclusions: The skin level of jaundice can be used as a rough guide in the estimation of total bilirubin in newborns with jaundice. This is especially useful in resource-limited setting where facilities for testing bilirubin level are lacking.

Bilateral oral leukoplakia: A case report and review on its potential for malignant transformation K Tupakula Pavan, Ankita Kar, S Reddy Sujatha, BK Devi Yashodha, Nagaraju Rakesh, V Shwetha International Journal of Clinicopathological Correlation 2018 2(2):27-30 Oral leukoplakia (OL) is considered as a most common potentially malignant disorder (PMD) affecting the mucosa of the oral cavity. With the passage of time, the definitions of OL kept evolving. Leukoplakia usually presents after the fourth decade of life and is one of the most common oral PMDs affecting the oral cavity. Based on the macroscopic features of OL, it can be classified into two subtypes: homogeneous and nonhomogeneous.

Clopidogrel-induced thrombotic thrombocytopenia after years of medication Rateesh Sareen, Menka Kapil, Piyush Mathur, Madhulika Sharma International Journal of Clinicopathological Correlation 2018 2(2):31-33 Thrombotic thrombocytopenic purpura (TTP) is a life threatening, fulminant disease characterized by fever, microangiopathy hemolytic anemia, thrombocytopenia, neurological signs and renal insufficiency. The real culprit is agglutinated platelets and fibrin which form micro thrombi, gets deposited in arterioles and capillaries without eliciting inflammatory response. The idiopathic cases of TTP are characterized by deficiency of ADAMTS-13 (a disintegrin and metalloprotease, with thrombospondin -1 like domains) metalloprotease activity. The use of antiplatelet drugs, the thienopyridine derivatives Clopidogrel & Ticlodipine, is associated with drug induced TTP. The literature studies indicate that most cases of thienopyridine associated TTP involve an antibody to ADAMTS-13 metalloprotease that cause thrombocytopenia and respond to therapeutic plasma exchange (TPE). We report a case of 59 year old male who was on Clopidogrel post coronary angioplasty since past five years. He presented to us with complaints of nose bleeding and renal insufficiency. The evaluation of this potentially fatal drug complication should be borne in mind by physicians for all patients receiving Clopidogrel treatment.

Endometrial osteocartilaginous metaplasia: A case report and review of the literature Yeo Yen Ching, Mihir Gudi, Josefa E.O Vella International Journal of Clinicopathological Correlation 2018 2(2):34-36 Rare cases of osseous metaplasia and a single case of cartilaginous metaplasia have been reported previously but no previously reported cases of osteo-cartilagenous metaplasia were found on searching the literature. Osteo-cartilagenous metaplasia is a benign lesion which may be treated successfully with hysteroscopy. Awareness of this condition by histopathologists is important in order to avoid misdiagnosis of endometrial malignant mixed mullerian tumour. The authors report a patient with endometrial osteo-cartilagenous metaplasia, describe the clinical and histological features and review the literature on this condition.

Dermatology, Venereology, Leprology

Medical device regulation in India: What dermatologists need to know Sandeep Lahiry, Rajasree Sinha, Suparna Chatterjee Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):133-137

Subclinical atherosclerosis and cardiovascular markers in patients with lichen planus: A case–control study Soheila Nasiri, Afsaneh Sadeghzadeh-Bazargan, Reza Mahmoud Robati, Hamid Reza Haghighatkhah, Shima Younespour Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):138-144 Background: Lichen planus is an idiopathic and chronic inflammatory disease that affects the skin and the mucous membranes, and has been associated with an increased risk for cardiovascular diseases. Hyperhomocysteinemia has been regarded as a risk factor for atherosclerosis and cardiovascular diseases. Increased plasma fibrinogen levels are also associated with increased risk of myocardial infarction. Objective: The main aim of this study is the evaluation of common carotid artery mean intima media wall thickness, serum fibrinogen and homocysteine levels in patients with lichen planus. Methods: Forty-three patients with lichen planus and 43 age, gender and body mass index (BMI) matched healthy controls (from general population without the disease) were included in this study. Results: Compared to the healthy controls, patients had statistically significant greater mean intima media wall thickness of the common carotid artery. Moreover, a positive correlation was observed between lichen planus and increased serum homocysteine and c-reactive protein levels. Limitations: The main limitation of this study is the small sample size due to the time limitation and financial constraints. Conclusion: Early diagnosis of atherosclerosis in patients with lichen planus might afford better prophylaxis, including weight control and/or lipid profile monitoring. Measurement of the mean intima media wall thickness of the common carotid artery by duplex high-resolution B-mode ultrasound scanning could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus.

Psoriasis increases the risk of concurrent inflammatory bowel disease: A population-based nationwide study in Korea Jin Yong Lee, Sungchan Kang, Jung Min Bae, Seong Jin Jo, Seong-Joon Koh, Hyun-Sun Park Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):145-152 Background: The epidemiology of the association between psoriasis and inflammatory bowel disease is poorly defined and remains controversial. Aim: To evaluate the prevalence of inflammatory bowel disease in patients with psoriasis compared with the general population. Methods: We searched the nationwide health claims database between 2011 and 2015 and evaluated the prevalence of inflammatory bowel disease, including Crohn's disease and ulcerative colitis. Results: Prevalence of inflammatory bowel disease, Crohn's disease and ulcerative colitis in patients with psoriasis vs the general population in 2011 were 0.16, 0.05 and 0.12% vs 0.08, 0.03 and 0.06%, respectively, which increased significantly with time between 2011 and 2015. Patients with psoriasis consistently revealed higher standardized prevalence (age and sex adjusted) of inflammatory bowel disease, Crohn's disease and ulcerative colitis compared with the general population. Subgroup analysis revealed the highest risk of prevalent inflammatory bowel disease in patients younger than 19 years (crude odds ratio 5.33, 95% confidence interval 3.74–7.59). Severe psoriasis demonstrated higher odds of inflammatory bowel disease (odds ratio 2.96, 95% confidence interval 2.54–3.45) than mild psoriasis (odds ratio 1.68, 95% confidence interval 1.51–1.88). Limitations: Limited data for doing adjustment and cross-sectional study design. Conclusions: Psoriasis patients revealed higher risk of inflammatory bowel disease. In particular, young patients and those with severe psoriasis may require closer monitoring and comprehensive management.

Linking of psoriasis with osteopenia and osteoporosis: A cross-sectional study Antonio Martinez-Lopez, Gonzalo Blasco-Morente, Maria Sierra Giron-Prieto, Miguel Angel Arrabal-Polo, Maria Luque-Valenzuela, Juan de Dios Luna-Del Castillo, Jesus Tercedor-Sanchez, Salvador Arias-Santiago Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):153-159 Background/Purpose: Psoriasis is a multisystem disease which has been related to vitamin-D deficiency through chronic inflammation. This psoriasis-related inflammatory state and vitamin-D deficiency may induce bone mineral density loss. The purpose of this study is to assess the relationship of psoriasis with bone mineral density, by comparing psoriatic patients with healthy controls and patients with osteopenia/osteoporosis. Methods: A total of 185 subjects were studied; 58 psoriatic patients who had not been under systemic or biological treatment were included. Age, gender, body mass index, phosphocalcic metabolic parameters and hip and lumbar (L4) bone mineral density data were collected. These variables were compared with those collected in 61 healthy controls and 67 patients with osteopenia/osteoporosis. Results: Psoriatic patients showed worse hip and lumbar spine bone mineral density levels than healthy controls (P = 0.001) and better levels than osteoporotic patients (P < 0.001). Multivariate analysis demonstrated a negative association of age and a positive association of body mass index in hip bone mineral density in psoriatic patients. Limitations: The main limitations are those of cross-sectional studies, such as a lack of follow up period, and a male predominance in the psoriatic group, which is corrected employing a multivariate analysis with an adjusted model for confounding factors. Conclusions: Bone mineral density levels in psoriatic patients are situated halfway between healthy controls and patients with osteopenia/osteoporosis. In addition, the higher body mass index in patients with psoriasis appears to confer a protective effect against further development of lower bone mineral density.

A randomized study to evaluate the efficacy and effectiveness of two sunscreen formulations on Indian skin types IV and V with pigmentation irregularities Rashmi Sarkar, Vijay Kumar Garg, Annie Jain, Divya Agarwal, Anupama Wagle, Frederic Flament, Michèle Verschoore Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):160-168 Background: Regular exposure to ultraviolet rays is high in India, where most Indians present Fitzpatrick skin phototypes IV and V. Aims: To evaluate the efficacy and compare the effectiveness of two sunscreen products on Indian skin types IV and V with pigmentation irregularities. Methods: A randomized, uncontrolled and investigator-blinded, single-center study enrolled adult men and women (18–45 years) with Fitzpatrick skin phototypes IV (28° < individual typological angle <10°) and V (10° < individual typological angle < −30°) with pigmentary abnormalities seen on the face in adults (actinic lentigines and postinflammatory hyperpigmentation), who did not use sunscreens. Participants were randomized (1:1) to either of the two marketed sunscreen products, Product A (sun protection factor 50 PA+++) or Product B (sun protection factor 19 PA+++), applied twice daily before sun exposure for ≥2 h. Primary objectives aimed at assessing possible improvement in hyperpigmented spots and overall skin appearance after 12 weeks of use. Evaluation of skin radiance and skin color was done by means of L'Oréal color chart and colorimetric measurements (Chromameter®). Results: Among the 230 enrolled participants, 216 (93.91%) completed the study. The clinical assessment of the density of pigmented spots and skin radiance showed significant (P < 0.001) improvement in both groups during all visits. The qualitative (participant perception) and quantitative (Chromameter®) data indicated improvement in pigmentation from Week 0 to Week 12. Both products were well-tolerated. Limitations: The study was conducted over a rather short period of time (12 weeks) at a single location. Conclusions: This is the first study conducted on Indian skin phototypes IV and V under real-life conditions. It demonstrated the effect of regular sunscreen usage in the prevention of certain signs of skin photoaging such as increased pigmentation or pigmentary abnormalities, thus providing support and assistance to clinicians in suggesting the use of efficient sun-screening products to patients.

Crusted nipple and areola: A new aetiology of secondary hyperkeratosis of the nipple and areola Dhaifallah A Alenizi Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):169-170 Hyperkeratosis of the nipple and areola is a rare condition first described by Tauber in 1923. Less than 100 cases have been reported in the literature. Hyperkeratosis of the nipple and areola presents as hyperkeratotic, hyperpigmented plaques on the nipple and areola. It is more common in females. An 18-year-old female patient presented with hyperkeratotic, plaque-like, hard crusts on both nipples and areolas. The examining physician could successfully remove this crust using his finger. The crust had accumulated as a result of the patient's reluctance to touch or clean the breast area due to psychological issues. A crusted nipple and areola may occur as a secondary condition due to a patient's reluctance to touch or clean their breasts.

Primary mucinous carcinoma of skin with a trichoadenomatous component: A rare case report Athota Kavitha, Chennamsetty Kavya, Kovi Sneha, Chennamsetty Teja Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):171-174 Primary mucinous carcinoma of the skin is a rare subtype of eccrine sweat gland tumors. Differentiating it from metastatic adenocarcinomas is important in the management of this condition. We report the case of a 55-year-old female presenting with a painless nodule, which was subsequently diagnosed as primary mucinous carcinoma of skin with a trichoadenomatous component. The possibility of a metastatic adenocarcinoma was ruled out by performing ultrasound abdomen, total body computed tomography, mammogram and colonoscopy.

Ultrasound assessment of enthesis thickness in psoriasis and psoriatic arthritis: A cross-sectional study Dario Graceffa, Claudio Bonifati, Viviana Lora, Pier Luigi Saraceni, Catia De Felice, Maria Sole Chimenti, Roberto Perricone, Aldo Morrone Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):175-181 Background: The inflammatory involvement of the enthesis in the course of psoriasis is accompanied by structural abnormalities detectable by ultrasound. The most common of these abnormalities is the thickening of the tendon at the insertion site. Aims: The aim of the present study was to compare the thickness of entheses of patients with psoriatic arthritis, only skin psoriasis, and healthy controls. Methods: A cross-sectional study was conducted in a cohort of patients affected with either only skin psoriasis or psoriatic arthritis as well as in a control group. Eight entheses sites were scanned by ultrasound bilaterally. The following entheseal characteristics were collected and recorded in a predefined database: entheseal thickness, bone erosions, enthesis calcifications (enthesophytes), presence of blood flow, and presence of bursitis. All the detected entheseal changes were scored, and the data was statistically analyzed. Results: The major differences in enthesis thickness between only skin psoriasis and psoriatic arthritis patients were found at the following sites: (i) olecranon tuberosity, (ii) superior pole of the patella, and (iii) medial epicondyle of femur. The thickness of the medial collateral ligament at the site of the femoral origin was increased in psoriatic arthritis, but not in both only skin psoriasis and healthy controls. The score obtained by adding the thickness of all the 8 examined entheses for each patient showed significant differences among the three groups (psoriatic arthritis: 81.3; only skin psoriasis 74.4; Controls: 67.6; P < 0.0001). Interestingly, we found that in psoriatic arthritis patients, the highest enthesis thickening was seen in entheses affected by bone erosions. Limitations: The small sample of patients studied is a limiting factor in this study. Conclusions: Our data demonstrated that the ultrasound measurement of the enthesis thickness enables a distinction between patients with psoriatic arthritis from those with only skin psoriasis. It is a useful method to improve diagnostic accuracy, especially in patients without clear clinical signs of enthesitis.

An observational study on glabellar wrinkle patterns in Indians Amala Kamat, Trisha Quadros Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):182-189 Background: Botulinum A exotoxin is an established treatment for glabellar frown lines, crow's feet, and horizontal furrows of the forehead. The glabella is probably the most common site for botulinum toxin treatment in Asians. Five glabellar contraction patterns have been classified in earlier studies based on eyebrow approximation, depression, and elevation. Unfortunately, this was found to be confusing by many practitioners. Indians, as all Asians, have smaller muscles compared to the European population, and there is no consensus on the optimal dosage per injection site or concentration of toxin to be used. Aims: (a) Identification and classification of glabellar wrinkle patterns in Indians. (b) Optimization of the minimal effective dose of toxin per site. Materials and Methods: Retrospective photographic analysis of 200 patients who received botulinum toxin for the first time to treat glabellar wrinkles was conducted. The wrinkle patterns were identified and classified by the authors based on the prevalence of perpendicular and transverse glabellar lines, nasal, and forehead wrinkles. Results: Six patterns were identified: (1) 11 (2) U (3) Pi (4) X (5) W (6) I. The relevant muscles were identified and doses optimized for those sites. Limitations: The doses mentioned in this study are not universal for all patients and toxin units would have to be altered and individualized according to the bulk of the facial muscles and individual needs. Conclusion: The investigators classification, injection patterns, and dosage may provide valuable guidance to facial esthetic treatment.

Onychomatricoma: Clinical, dermoscopy and ultrasound findings Denise Gamé, Ane Jaka, Carlos Ferrándiz Indian Journal of Dermatology, Venereology, and Leprology 2019 85(2):190-191

Global Infectious Diseases

State of the globe: Effect of pneumococcal conjugate vaccines on nonvaccine-type invasive pneumococcal disease Sunil Kumar Raina Journal of Global Infectious Diseases 2019 11(1):1-1

Treating more with less: Effectiveness and event outcomes of antituberculosis fixed-dose combination drug versus separate-drug formulation (Ethambutol, Isoniazid, Rifampicin and Pyrazinamide) for pulmonary tuberculosis patients in real-world clinical practice Jacqueline Mui Lan Lai, Su Lan Yang, Richard Avoi Journal of Global Infectious Diseases 2019 11(1):2-6 Introduction: Conventionally, a combination of four separate drugs (ethambutol, isoniazid, rifampicin, and pyrazinamide [EHRZ]) is the first-line pharmacotherapy for pulmonary tuberculosis (TB). In recent years, fixed-dose combination (FDC) formulation, where a single tablet contains the active ingredients of four aforementioned drugs, is gaining popularity due to its ease of administration. Objective: To compare the real-world effectiveness of EHRZ and FDC treatment groups on a cohort registry by investigating the sputum conversion rate and treatment outcomes of both groups. Methods: A total of 11,489 patients' data were extracted from the Sabah TB registry between January 2012 and June 2016, including EHRZ (n = 4188) and FDC (n = 7301) patients. Then, 1:1 propensity score matching was adopted to reduce the baseline bias. Caliper matching was conducted with maximum tolerance score set at 0.001. Confounders included in the propensity score matching were gender, nationality, diabetes, HIV status, smoking status, and chest X-ray status. Successful matching provided 4188 matched pairs (n = 8376) for final analysis. Results: In this matched cohort of 4188 pairs, the 2-month sputum conversion rate of FDC group was significantly higher than the EHRZ group (96.3% vs. 94.3%; P < 0.001) whereas 6-month sputum conversion of both groups showed no significant difference. Treatment outcomes such as noncompliance rate, failure rate, and success rate have no significant difference (P > 0.05) in both the treatment groups. There was an incidental finding of reduced death rate among FDC group compared to the EHRZ group (0.2% vs. 0.5%; P = 0.034). Conclusion: The FDC formulation has better sputum conversion rate at 2 months compared to conventional EHRZ regime as separate-drug formulation. It was also observed that FDC has a slight protective effect against all-cause death among TB patients. This protective effect of FDC, however, still needs to be proven further.

Clinico-epidemiological study of viral acute encephalitis syndrome cases and comparison to nonviral cases in children from Eastern India Sandeep Kumar Tripathy, Pravakar Mishra, Bhagirathi Dwibedi, Lipsa Priyadarshini, Rashmi Ranjan Das Journal of Global Infectious Diseases 2019 11(1):7-12 Objectives: The objective is to study the clinico-epidemiological features of viral acute encephalitis syndrome (AES) cases and compare them with nonviral AES cases in children from Eastern India. Methods: This prospective observational study was conducted in the department of pediatrics of a tertiary care teaching hospital in Eastern India over 18-month period. Children (6 months to 15 years) with acute onset of fever (≥37.5°C) and a change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk) and/or new onset of seizures (excluding simple febrile seizures) were included in the study. The main outcome measures were the etiology and proportion attributed to viruses causing AES with clinical correlation. Results: Of 834 of clinically suspected AES cases, viral etiology could be confirmed in 136 (16.3%) cases (herpes simplex virus-1 [HSV-I] was most common). The 5–15 years' age group was most commonly affected (boys > girls). More cases occurred from July to November. The presence of rash and Glasgow Coma Scale <8 at admission was significantly higher in viral AES. During hospitalization, development of shock, ventilatory requirement, duration of stay, and mortality was significantly higher in viral AES. On neuroimaging, global cerebral injury was common in HSV, Japanese encephalitis, and varicella-virus AES. Conclusions: Viral etiology forms a significant proportion of pediatric AES. Morbidity and mortality are high in viral compared to nonviral AES. Herpes encephalitis (HSV-I) is the most common cause of pediatric AES in Eastern India. Viral AES has poor prognosis compared to nonviral AES.

Factors associated with mortality in immunocompetent patients with hospital-acquired pneumonia Pavaruch Sangmuang, Aroonrut Lucksiri, Wasan Katip Journal of Global Infectious Diseases 2019 11(1):13-18 Aim: The aim of the study is to determine the factors associated with 28-day mortality in immunocompetent patients with hospital-acquired pneumonia (HAP). Methods: This was a 42-month retrospective cohort study in Chiang Kham Hospital. Patients with HAP diagnosed between January 2013 and June 2016 who did not have an immunocompromised status were recruited into the study. Statistical Analysis Used: Univariable and multivariable binary logistic regression analyses were performed to determine the factors associated with mortality in patients with HAP. Results: A total of 181 HAP patients. The most causative pathogens were nonfermenting Gram-negative bacilli. Fifty-two (28.7%) patients had died within 28 days after HAP diagnosis. Multivariable analysis demonstrated that mechanical ventilation (MV) dependency (adjusted odds ratio [OR] = 3.58, 95% confidence interval [CI] 1.53–8.37, P = 0.003), antibiotic duration (adjusted OR = 0.79, 95% CI 0.70–0.88, P < 0.001), acute kidney injury (adjusted OR = 5.93, 95% CI 1.29–27.22, P = 0.022), and hematologic diseases (adjusted OR = 11.45, 95% CI 1.61–81.50, P = 0.015) were the significant factors associated with 28-day mortality. Conclusions: The factors associated with mortality were MV dependency, HAP duration of treatment, acute kidney injury, and hematologic disease. Early recognition of these factors in immunocompetent patients with HAP and treatment with intensive care may improve the outcome.

Co-infection of herpes simplex virus type 2 and HIV infections among pregnant women in Ibadan, Nigeria Chinenye Gloria Anaedobe, Tinuade Adesola Ajani Journal of Global Infectious Diseases 2019 11(1):19-24 Introduction: Genital infection with herpes simplex virus type 2 (HSV-2) facilitates the acquisition of HIV, both mutually reinforcing infection. Lifelong latent HSV-2 infection raises concerns among women of reproductive age, considering the risk of neonatal transmission. In Nigeria, screening for HSV-2 and co-infection with HIV in antenatal clinics is not routine. This study was undertaken to determine the seroprevalence and co-infection of HSV-2 and HIV among pregnant women. Methods: This was a cross-sectional study conducted at the antenatal clinic of the University College Hospital, Ibadan, between March and August 2013. A total of 270 consenting pregnant women were enrolled. The study involved collecting socio-demographic data and laboratory determination of HSV-2 immunoglobulin G (IgG) and HIV seroprevalence using type-specific third-generation enzyme-linked immunosorbent assay (DIAPRO Diagnostic Bioprobes, Milan, Italy) and Uni-Gold Recombigen/ALERE determine, respectively. Data analyses were done using SPSS version 20 (SPSS Inc., IL, USA). Results: The seroprevalence for HSV-2 type-specific IgG was 33.3% (90/270), and HIV antibodies were identified in 19.63% (53/270) of the women. The HIV co-infection was 38.8% (35/90) among HSV-2-positive women and 10% (18/180) among HSV-2-negative women. Majority of the HSV-2 positive women (62.2%, 56/90) presented in their 2nd trimester while 18.9% (17/90) in their 3rd trimester. Conclusion: The seroprevalence of HSV-2 in this pregnant population is lower than what is observed in some other Sub-Saharan African countries; however, HSV-2/HIV co-infection is high. The HSV-2-seronegative women are still susceptible to primary HSV-2 infection in pregnancy with increased risk for HIV co-infection and neonatal transmission.

Analysis of anti-toxoplasma immunoglobulin G and immunoglobulin M antibody levels after intervention with Curcuma Longa extract on early pregnant mice with acute toxoplasmosis Tigor Peniel Simanjuntak, Mochammad Hatta, Andi M Tahir, Robert H Sirait, Marni B Karo, Titus Tambaib, Ressy Dwiyanti, Rizki Amelia Noviyanthi, Ade Rifka Junita Journal of Global Infectious Diseases 2019 11(1):25-29 Background: Curcuma longa has strong anti-inflammatory effect. This study aims to evaluated the level of anti-Toxoplasma immunoglobulin G and immunoglobulin M (IgG-IgM) antibody after intervention with C. longa extract in early pregnant mice with acute toxoplasmosis. Materials and Methods: We evaluated 20 early pregnant mice that were divided into five groups, four mice in each. Group 1-4 received injections of Toxoplasma gondii tachyzoites. Three days later, G1 and G2 were given orally 125 mg/kg/day and 500 mg/kg/day of C. longa extract, respectively. G3 was given 60 mg/kg/day of spiramycin (positive control), and G4 was given 0.2 ml of distilled water (negative control). G5 underwent no intervention at all. Blood samples were obtained serially (before and 3 days after injection of tachyzoites, 3 days and 7 days after intervention) to assess anti-Toxoplasma IgG-IgM antibody levels by enzyme-linked immunosorbent assay methods. Results: Anti-Toxoplasma IgG-IgM antibody levels increased significantly 3 days after injection of tachyzoites (P < 0.05), but decreased significantly (P < 0.05) 3 days, and 7 days after administration of C. longa extract dose 125 mg, 500 mg, and spiramycin 60 mg, and there was no significant difference between these three groups. Anti-Toxoplasma IgG-IgM antibody levels increased significantly (P < 0.05) 3 days, 6 days, and 10 days after injections of tachyzoites on G4. The IgG-IgM antibody levels fluctuated on G5 and considered as insignificant (P > 0.05). Conclusion: The administration of C. longa extract at a dose of 125 mg/kg/day for 7 days effectively decreased anti-Toxoplasma IgG-IgM antibody level in early pregnant mice with acute toxoplasmosis.

Changes in the pneumococcal vaccine serotypes in adult noninvasive pneumonia after the introduction of pneumococcal conjugate vaccination for children Hiroaki Takeda, Chisa Sato, Chang Bin, Midori Nishidzuka, Mari Watanabe, Tomoka Yamamoto, Hiroki Suzuki, Kazunori Oishi, Fumihiro Tsuchida Journal of Global Infectious Diseases 2019 11(1):30-35 Context: Although the incidence of invasive pneumococcal infections in children has decreased since the introduction of pneumococcal conjugate vaccines (PCVs), the appearance of serotype replacements has continued to increase. Aims: We examined the frequency of serotype replacements in adult cases of pneumococcal pneumonia. Furthermore, the transition in the coverage of vaccine serotypes (VTs) to non-VTs (NVTs) was also examined. Settings and Design: We investigated all confirmed cases of pneumococcal pneumonia in 303 adult patients admitted to Yamagata Saisei Hospital between April 2006 and March 2015. Materials and Methods: Pneumococcal serotypes were determined by testing for a specific type of antiserum using the capsular swelling method. Statistical Analysis Used: Chi-square tests were used to compare patient characteristics. Results: Annually, the number of admitted patients ranged from 24 to 43, with most of them being men (64.7% of the total patient cohort). Although many cases involved some underlying conditions, the rate of pneumococcal vaccination remained low. The average rate of multigeneration housing was high (37.6%). The rates of pneumococcal vaccine coverage declined since 2013 (7-valent PCV (PCV7), 18.5%; PCV13, 59.3%; and 23-pneumococcal polysaccharide vaccine (PPSV23), 66.7%) and were <50% for each vaccine (PCV7, 4.7%; PCV13, 32.6%; and PPSV23, 48.8%) in 2015. In addition, the VTs were replaced with NVTs in 2015 (48.8% vs. 51.2%). Conclusions: The frequency of NVTs in adult pneumococcal pneumonia increased in 2013, with the frequency exceeding that of the vaccine forms in 2015. Regular PCV vaccination of children and multigeneration housing seem to be associated with this reversed trend.

Global contributors to antibiotic resistance Aastha Chokshi, Ziad Sifri, David Cennimo, Helen Horng Journal of Global Infectious Diseases 2019 11(1):36-42 Introduction: Antibiotic-resistant infections have become increasingly prevalent nowadays. As a result, it is essential to examine the key socioeconomic and political factors which contribute to the rise in the prevalence of antibiotic resistance in developing and developed nations. This study aims to identify the various contributors to the development of antibiotic resistance in each type of nation. Methods: PUBMED was used to identify primary research, systematic reviews, and narrative reviews published before Jan 2017. Search terms included antibiotic resistance, antimicrobial resistance, superbugs, multidrug-resistant organisms, developing countries, developed countries. Publications from different countries were included to ensure generalizability. Publications were excluded if they didn't mention factors causing resistance, focused on the molecular basis of resistance, or if they were case reports. Publicly available reports from national and international health agencies were used. Results: In developing countries, key contributors identified included: (1) Lack of surveillance of resistance development, (2) poor quality of available antibiotics, (3) clinical misuse, and (4) ease of availability of antibiotics. In developed countries, poor hospital-level regulation and excessive antibiotic use in food-producing animals play a major role in leading to antibiotic resistance. Finally, research on novel antibiotics is slow ing down due to the lack of economic incentives for antibiotic research. Conclusion: Overall, multiple factors, which are distinct for developing and developed countries, contribute to the increase in the prevalence of antibiotic resistance globally. The results highlight the need to improve the regulatory framework for antibiotic use and research globally.

Fatal oculocutaneous ecthyma gangrenosum in human immunodeficiency virus/acquired immunodeficiency syndrome: Case report and review of the literature Eshan B Henshaw, Affiong A Ibanga, Derima P Obaji Journal of Global Infectious Diseases 2019 11(1):43-46 Ecthyma gangrenosum (EG) is a rare, infective skin disease, predominantly but not exclusively caused by Pseudomonas aeruginosa. It is often seen in individuals with immunosuppression, although it has also been reported among previously healthy individuals. It was initially thought to be pathognomonic of P. aeruginosa septicemia, but this assertion was discarded following several reports on EG without bacteremia and EG with varied bacterial and fungal etiologies. There are scant reports of its association with human immunodeficiency virus (HIV) infection, while ocular involvement is extremely rare. An extensive search of the literature also found no report on EG, nor its relationship with HIV/acquired immunodeficiency syndrome (AIDS) from Sub-Saharan Africa. We hereby present a fatal case of multiple EG lesions in a 44-year-old Nigerian female with AIDS in the absence of bacteremia and review the literature of its association with HIV/AIDS and its concurrent orbital involvement.

Recurrence of Citrobacter koseri-associated intra-abdominal infection 2 years after spilled gallstones during laparoscopic cholecystectomy Kelly Cummings, Teresa Khoo, Timothy Pal, George Psevdos Journal of Global Infectious Diseases 2019 11(1):47-49 Spilled gallstones during laparoscopic cholecystectomy (LC) are common. Lost gallstones can lead to complications such as intra-abdominal abscesses, which can occur days, months, or even years after the procedure. Citrobacter koseri belongs to the family of Enterobacteriaceae. It is a low-virulence pathogen; however, it is linked to infections of the urinary tract and abdomen. We report the case of a 70-year-old diabetic male who presented with C. koseri- associated subhepatic abscess. Two years prior, he had emphysematous cholecystitis and liver abscess caused by C. koseri. During his LC, gallstones were spilled in the abdominal cavity and every effort was made to retrieve them. However, 2 years later, an aspiration of the subhepatic abscess revealed cholesterol fragments. We hypothesize that dislodged cholesterol gallstones and bile, contaminated with C. koseri, were the culprits for the appearance of the subhepatic abscess with the same organism 2 years after the LC.

Homoeopathy

Popularity, safety and quality of homoeopathic medicines Raj K Manchanda Indian Journal of Research in Homoeopathy 2018 12(4):191-193

An open-label pilot study to identify the usefulness of adjuvant homoeopathic medicines in the treatment of cerebral stroke patients Aslam Abbas, Md Shahid Ali, Hima Bindu Ponnam, Divya Taneja, Anil Khurana, Chaturbhuja Nayak, Anil Santapur Indian Journal of Research in Homoeopathy 2018 12(4):194-201 Background: Stroke, the third leading cause for neurological morbidity and mortality has a global annual incidence of 0.2–2.5/1000 population. The clinical sequelae of stroke are often devastating with hemiparesis, depression, walking difficulties and aphasia. It is essential to take measures halting the progression of stroke. Homoeopathic literature mentions many medicines for stroke. Till a pilot study was undertaken to study the usefulness of Homoeopathy as an adjuvant therapy to standard conventional care in stroke patients. Materials and Methods: An open-label pilot study was conducted at Princess Durru Shehvar Children's and General Hospital, Hyderabad, in coordination with Extension Clinical Research Unit of Central Council for Research in Homoeopathy. Fifty patients presenting with episodes of cerebral stroke of the different period were assessed by the National Institute of Health Stroke Scale (NIHSS) Score, prior homoeopathic treatment and after 6 months of treatment. Results: Of 50 patients, 10 patients had stroke more than 1 year and suffering with sequelae, 27 patients had stroke episode between 1 month and 1 year and 13 patients had a stroke episode within 4 weeks. The reduction in NIHSS score after 6 months of treatment was statistically significant in all three groups. The useful medicines found were Causticum (n = 11), Arnica montana (n = 7), Nux vomica (n = 6), Lycopodium (n = 6) and Lachesis (n = 3). Neither patient had worsening signs nor any new infarcts during the study. Conclusion: This pilot study showed encouraging results. Further randomised control trials are suggested to evaluate the efficacy of homoeopathic medicines in stroke.

Homoeopathic drug dilutions of Thuja occidentalis attenuate complete Freund's adjuvant-induced arthritis in Wistar rats Sachin S Patil, Umesh B Mahajan, Sameer N Goyal, Sateesh Belemkar, Chandragouda R Patil Indian Journal of Research in Homoeopathy 2018 12(4):202-211 Context: Thuja occidentalis is prescribed in Homoeopathy in treating rheumatoid arthritis. We speculated the anti-arthritic mechanism of Homoeopathic dilutions of Thuja occidentalis against the complete Freund's adjuvant (CFA)-induced arthritis in rats. Materials and Methods: Arthritis was induced (n = 28) by subplantar injection of 0.1 ml CFA in the right hind paw of rats. The oral dose of crude Thuja occidentalis was 30 mg/kg/b. i. d and that of Homoeopathic dilutions was 0.1 ml/b. i. d. Orally administered diclofenac at 5 mg/kg/day served as a standard. The treatments continued for 24 days. The severity of arthritis was determined weekly as rise in paw volume, mechanical allodynia and changes in body weight. On the 25th day, X-ray imaging of the arthritic paws was recorded, and the biopsy samples extracted from the paws were subjected to the estimation of pro-inflammatory cytokines and histological evaluations. Results: Thuja occidentalis Homoeopathic dilutions and its crude form protected rats against the CFA-induced arthritic lesions. The mother tincture, 6cH, 30cH and 200cH dilutions of Thuja occidentalis significantly reduced the CFA-induced rise in paw volume, reduced the mechanical allodynia and also reduced the levels of interleukin (IL) IL-1, IL-6 and tumour necrosis factor alpha in paw tissue. CFA-induced articular changes, oedema, cellular infiltrations and cartilage damage were reduced by Thuja occidentalis dilutions. The radiological images indicated that Thuja occidentalis treatment reduced the CFA-induced joint swelling, bone erosion and joint space narrowing. Conclusion: Our findings substantiate the anti-arthritic effects of Thuja occidentalis Homoeopathic dilutions against CFA-induced arthritis and indicate that Homoeopathic dilutions of Thuja occidentalis, particularly 6cH dilution, exert more potent anti-arthritic effects than its crude form.

Chemoprofiling of homoeopathic drug Holarrhena antidysenterica L. Rakhi Mishra, Manoj Kumar, Binit Dwivedi, BS Arya, Renu Arya, Anil Khurana, Raj K Manchanda Indian Journal of Research in Homoeopathy 2018 12(4):212-219 Background: Chemoprofiling of homoeopathic drug/tincture (HT) represents a comprehensive approach for evaluation of quality, purity, safety and efficacy of HT. This paper reflects the chemoprofiling of Homoeopathic drug Holarrhena antidysentrica L. Objective: The objective of this study is to standardise Holarrhena antidysenterica mother tincture by taking the samples from four different sources: Dr D. P. Rastogi, CRI (H) Noida (A) and three from market (labelled as B, C and D). Materials and Methods: The authentic sample of bark of Holarrhena antidysenterica supplied by the Centre of Medicinal Plants Research in Homoeopathy, Emerald, Tamil Nadu, India was used to prepare the mother tincture (as per the Homoeopathic Pharmacopoeia of India). The solvents used throughout the study, namely, ethanol, high-pressure liquid chromatography water, cyclohexane, chloromethane and diethylamine, were of analytical grade purity (MERCK Ltd.). Physicochemical properties, ultraviolet (UV) spectroscopy and high-performance thin-layer chromatography (HPTLC) chemoprofile of raw drug and mother tinctures were standardised and compared with market samples. Results: The present study reveals the moisture content (14.40%), total ash (4.65%), alcohol (18.0%), water extractive values (16.0%), total solids (1.47%), weight/ml (0.92 g) and alcohol content (60.6%). In UV spectroscopy, λmaxvalues were observed at 228 and 278 nm in HT. HPTLC analysis of in-house HT (A) and three market samples (B, C, D) was performed by using cyclohexane: chloromethane: diethylamine (7:3:1, v/v/v) as mobile phase. Under UV light (254, 366 nm) and in the presence of visualising agent Dragendroff, bands of active constituent were observed in all the four samples. However, excess amount of active constituents were found in in-house HT (a) rather than the market samples (B, C and D). Conclusion: The present physicochemical and phytochemical data may be considered as pharmacopoeia standards for the homoeopathic drug Holarrhema antidysentrica L.

World Integrated Medicine Forum 2017: A feedback survey analysis Anupriya Chaudhary, Harleen Kaur, Jyoti Sachdeva, Mohua Dutta, Anil Khurana, Robbert van Haselen, Raj K Manchanda Indian Journal of Research in Homoeopathy 2018 12(4):220-230 Introduction: The first-of-its-kind World Integrated Medicine Forum (WIMF) on the regulation of homoeopathic medicinal products (HMPs) which was attended by various stakeholders from 23 countries witnessed rigorous discussions to strengthen existing regulatory framework of homoeopathic medicines in the world, as well as to bring harmony within the Homoeopathy market for drug manufacture standards including pharmacopoeial convergence. Materials and Methods: A feedback questionnaire was shared with the participants through SurveyMonkey online platform to seek their opinion about the Forum, obtain their country-specific views about regulations of HMPs, to evaluate the extent to which the Forum could meet its objectives and also to identify areas of improvements which may be taken note for organising a future WIMF. Results: Sixty-one percent participants from 18 countries returned the survey. Analysis of the responses revealed a group consensus about the remarkable organisation of the Forum, its usefulness from a national perspective, etc. The questions could also fetch insight about country-specific reforms that are required in the availability and regulations of HMPs. All the respondents who took the survey recommended a next Forum on the same lines, out of which 92% said they would recommend it to other colleagues. Conclusion: Homoeopathy is a widely recognised and accepted system worldwide. Based on its increasing demand, a harmonised regulatory system for homeopathic medicines must be developed to ensure good quality of HMPs, and this can be achieved through cooperative interactions among various stakeholders, both nationally and globally. A Forum such as this, at least once every 2 years, can provide the right push on this front.

Effect of individualised Homoeopathy in the treatment of infertility Suraia Parveen, Himadri Bhaumik Indian Journal of Research in Homoeopathy 2018 12(4):231-239 A 37-year-old woman, being married for 6 years, presented to the homoeopathic outpatient department, after treatment of infertility by a gynaecologist for few years. She had a past history of emergency ovarian cystectomy for endometriosis 1 year after her marriage. Her subsequent infertility workup revealed hydrosalpinx with one-sided tubal block along with the evidence of poor ovarian reserve. Her husband's semen analysis was normal and was advised for donor-ovum in vitro fertilisation. At this point, she was treated with constitutional homoeopathic medicine following the miasmatic analysis with the holistic concept of Homoeopathy over 6 months. Treatment started with Silicea and later switched to Syphilinum. She conceived normally after that and subsequently delivered a healthy baby at full term. This case shows the positive role of classical homoeopathic treatment on subfertility.

Republication-predatory journals: A downside on research and hampering the impact and relevance of scientific outcome NC Jain, Ginu Suhail Khan Indian Journal of Research in Homoeopathy 2018 12(4):240-247 The advancement of medical knowledge is quintessentially based on the authentic and reliable scientific research and publications. This is in addition to the recently mandated requirement of original research publications in indexed journals to ensure career progression in academic/medical institutions; thus, the need for ‘publications’ in scientific medical scholarly journals has increased substantially. On the other hand, this has given an unparalleled rise in the number of standalone journals and publishers ‘predatory’ is the term, who are ready to process the manuscripts on priority with almost guaranteed publication, at a cost, but having no credibility to the research being published. To foster awareness creation among students at the post-graduate level and for faculty of medical colleges and research institutions, it has become very important to avoid these predatory journals. It is high time that the thinking among researchers of ‘publish or perish’ be changed to ‘Publish and Flourish’ by adopting stringent measures which have evolved over time to curtail this birch of predatory publishing. Researchers should now take the road less travelled. This review article aims to highlight all the relevant and important points about the threats posed by predatory journals and also suggests possible ways to overcome them. Republished with permission from: Jain NC, Khan GS. Predatory Journals: A Downside on Research and Hampering the Impact and Relevance of Scientific Outcome. RUHS J Health Sci 2018;3:99-105.

Obituary of Dr. Upma Bagai Sukhbir Kaur Indian Journal of Research in Homoeopathy 2018 12(4):248-249 Dr. Upma Bagai left for her heavenly abode on 8 September 2018. At the time of her untimely demise, she was serving as Professor and Chairperson, Department of Zoology, Panjab University, Chandigarh.

Erratum: Homoeopathic treatment for lower urinary tract symptoms in men with benign prostatic hyperplasia: An open label randomised multicentric placebo-controlled clinical trial Indian Journal of Research in Homoeopathy 2018 12(4):250-250