Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Possible treatment and strategies for COVID-19: review and assessment.

The coronavirus disease 2019 (COVID-19) is declared as an international emergency in 2020. Its prevalence and fatality rate are rapidly increasing but the medication options are still limited for this perilous disease. The emergent outbreak of COVID-19 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) keeps propagating globally. The present scenario has emphasized the requirement for therapeutic opportunities to relive and overcome this latest pandemic. Despite the fact, the deteriorating developments of COVID-19, there is no drug certified to have considerable effects in the medical treatment for COVID-19 patients. The COVID-19 pandemic requests for the rapid testing of new treatment approaches. Based on the evidence, hydroxychloroquine is the first medicine opted for the treatment of disease. Umifenovir, remdesivir, and fevipiravir are deemed the most hopeful antiviral agent by improving the health of infected patients. The dexamethasone is a first known steroid medicine that can save the lives of seriously ill patients, and it is shown in a randomized clinical trial by the United Kingdom that it reduced the death rate in COVID-19 patients. The current review recapitulates the existing evidence of possible therapeutic drugs, peptides, humanized antibodies, convulsant plasma, and vaccination that has revealed potential in fighting COVID-19 infections. Many randomized and controlled clinical trials are taking place to further validate these agent's safety and effectiveness in curing COVID-19.

Realization of a push-me-pull-you swimmer at low Reynolds numbers.

Locomotion at low Reynolds numbers encounters stringent physical constraints due to the dominance of viscous over inertial forces. A variety of swimming microorganisms have demonstrated diverse strategies to generate self-propulsion in the absence of inertia. In particular, ameboid and euglenoid movements exploit shape deformations of the cell body for locomotion. Inspired by these biological organisms, the 'push-me-pull-you' (PMPY) swimmer (Avron J Eet al2005New J. Phys.7234) represents an elegant artificial swimmer that can escape from the constraints of the scallop theorem and generate self-propulsion in highly viscous fluid environments. In this work, we present the first experimental realization of the PMPY swimmer, which consists of a pair of expandable spheres connected by an extensible link. We designed and constructed robotic PMPY swimmers and characterized their propulsion performance in highly viscous silicone oil in dynamically similar, macroscopic experiments. The proof-of-concept demonstrates the feasibility and robustness of the PMPY mechanism as a viable locomotion strategy at low Reynolds numbers.

Imaging quantum fluctuations near criticality.

A quantum phase transition (QPT) occurs between two competing phases of matter at zero temperature, driven by quantum fluctuations. Though the presence of these fluctuations is well established, they have not been locally imaged in space and their local dynamics has not been studied so far. We use a scanning superconducting quantum interference device to image quantum fluctuations in the vicinity of the QPT from a superconductor to an insulator. We find fluctuations of the diamagnetic response in both space and time that survive well below the transition temperature, demonstrating their quantum nature. The fluctuations appear as telegraph-like noise with a range of characteristic times and a non-monotonic temperature dependence, revealing unexpected quantum granularity. The lateral dimension of these fluctuations grows towards criticality, offering a new measurable length scale. Our results provide physical insight about the reorganization of phases across a QPT, with implications for any theoretical description. This paves a new route for future quantum information applications.

Particle-Hole Character of the Higgs and Goldstone Modes in Strongly Interacting Lattice Bosons.

We study the low-energy excitations of the Bose-Hubbard model in the strongly interacting superfluid phase using a Gutzwiller approach. We extract the single-particle and single-hole excitation amplitudes for each mode and report emergent mode-dependent particle-hole symmetry on specific arc-shaped lines in the phase diagram connecting the well-known Lorentz-invariant limits of the Bose-Hubbard model. By tracking the in-phase particle-hole symmetric oscillations of the order parameter, we provide an answer to the long-standing question about the fate of the pure amplitude Higgs mode away from the integer-density critical point. Furthermore, we point out that out-of-phase symmetric oscillations in the gapless Goldstone mode are responsible for a full suppression of the condensate density oscillations. Possible detection protocols are also discussed.

Marine Microbes as a Potential Source of Cellulolytic Enzymes.

Marine environment hosts the wide range of habitats with remarkably high and diverse microbial populations. The ability of marine microorganisms to survive in extreme temperature, salinity, and pressure depends on the function of multivarious enzyme systems that in turn provide vast potential for biotechnological exploration studies. Therefore, the enzymes from marine microorganism represent novel bio catalytic potential with stable and reliable properties. Microbial cellulases constitute a major group of industrial enzymes that find applications in various industries. Majority of cellulases are of terrestrial origin, and very limited research has been carried out to explore marine microbes as a source of cellulases. This chapter presents an overview about the types of marine polysaccharases, classification and potential applications of cellulases, different sources of marine cellulases, and their future perspectives.

Emergence of coherence in the charge-density wave state of 2H-NbSe2.

A charge-density wave (CDW) state has a broken symmetry described by a complex order parameter with an amplitude and a phase. The conventional view, based on clean, weak-coupling systems, is that a finite amplitude and long-range phase coherence set in simultaneously at the CDW transition temperature T(cdw). Here we investigate, using photoemission, X-ray scattering and scanning tunnelling microscopy, the canonical CDW compound 2H-NbSe2 intercalated with Mn and Co, and show that the conventional view is untenable. We find that, either at high temperature or at large intercalation, CDW order becomes short-ranged with a well-defined amplitude, which has impacts on the electronic dispersion, giving rise to an energy gap. The phase transition at T(cdw) marks the onset of long-range order with global phase coherence, leading to sharp electronic excitations. Our observations emphasize the importance of phase fluctuations in strongly coupled CDW systems and provide insights into the significance of phase incoherence in 'pseudogap' states.

Pathology of advanced buccal mucosa cancer involving masticator space (T4b).

BACKGROUND: Buccal mucosa cancer involving masticator space is classified as very advanced local disease (T4b). The local recurrence rate is very high due to poor understanding of the extent of tumor spread in masticator space and technically difficult surgical clearance. The objective of this study is to understand the extent of tumor spread in masticator space to form basis for appropriate surgical resection. MATERIALS AND METHODS: All consecutive patients with T4b-buccal cancer underwent compartment resection, with complete anatomical removal of involved soft-tissue structures. Specimens were systematically studied to understand the extent of invasion of various structures. The findings of clinical history, imaging and pathologic evaluation were compared and the results were evaluated. RESULTS: A total of 45 patients with advanced buccal cancer (T4b) were included in this study. The skin, mandible and lymph nodes were involved in 30, 24 and 17 cases respectively. The pterygoid muscles were involved in 34 cases (medial-pterygoid in 12 and both pterygoids in 22 cases) and masseter-muscle in 32 cases. Average distance for soft-tissue margins after compartment surgery was 2 cm and the margins were positive in 3 cases. The group with involvement of medial pterygoid muscle had safest margin with compartment surgery while it was also possible to achieve negative margins for group involving lateral pterygoid muscle and plates.The involvement of pterygomaxillary fissure was area of concern and margin was positive in 2 cases with one patient developing local recurrence with intracranial extension. At 21 months median follow-up (13-35 months), 38 patients were alive without disease while two developed local recurrence at the skull base. CONCLUSIONS: T4b buccal cancers have significant soft-tissue involvement in the masticator space. En bloc removal of all soft-tissues in masticator space is advocated to remove tumor contained within space. The compartment surgery provides an opportunity to achieve negative margins for cancers actually contained within masticator space.It is inappropriate to club all patients with masticator space involvement in one group.

Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection.

Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies. We randomly assigned 317 subjects to a derivation or validation cohort. BAL samples were classified into four groups: infection, rejection grade ≥A1, both or neither. We employed generalized estimating equation and survival modeling to identify clinical predictors of rejection and infection. We found that CD25(+) and natural killer cell percentages identified a twofold increased odds of rejection compared to either the infection or the neither infection nor rejection groups. Also, monocytes, lymphocytes and eosinophil percentages were independently associated with rejection. A four-predictor scoring system had high negative predictive value (96-98%) for grade ≥A2 rejection, predicted future rejection in the validation cohort and predicted increased risk of bronchiolitis obliterans syndrome in otherwise benign samples. In conclusion, BAL cell immunophenotyping discriminates between infection and acute rejection and predicts future outcomes in lung transplant recipients. Although it cannot replace histopathology, immunophenotyping may be a clinically useful adjunct.

RRP1B is a metastasis modifier that regulates the expression of alternative mRNA isoforms through interactions with SRSF1.

RRP1B (ribosomal RNA processing 1 homolog B) was first identified as a metastasis susceptibility gene in breast cancer through its ability to modulate gene expression in a manner that can be used to accurately predict prognosis in breast cancer. However, the mechanism(s) by which RRP1B modulates gene expression is currently unclear. Many RRP1B binding candidates are involved in alternative splicing, a mechanism of gene expression regulation that is increasingly recognized to be involved in cancer progression and metastasis. One such target is SRSF1 (serine/arginine-rich splicing factor 1) (SF2/ASF, splicing factor 2/alternative splicing factor), an essential splicing regulator that also functions as an oncoprotein. Earlier studies demonstrated that splicing and transcription occur concurrently and are coupled processes. Given that RRP1B regulates transcriptional activity, we hypothesized that RRP1B also regulates the expression of alternative mRNA isoforms through its interaction with SRSF1. Interaction between RRP1B and SRSF1 was verified by coimmunoprecipitation and coimmunofluorescence. Treatment of cells with transcriptional inhibitors significantly increased this interaction, demonstrating that the association of these two proteins is transcriptionally regulated. To assess the role of RRP1B in the regulation of alternative isoform expression, RNA-sequencing data were generated from control and Rrp1b-knockdown cells. Knockdown of Rrp1b induced a significant change in isoform expression in over 600 genes compared with control cell lines. This was verified by quantitative reverse-transcription PCR using isoform-specific primers. Pathway enrichment analyses identified cell cycle and checkpoint regulation to be those most affected by Rrp1b knockdown. These data suggest that RRP1B suppresses metastatic progression by altering the transcriptome through its interaction with splicing regulators such as SRSF1.

Optimizing multimodality treatment for head and neck cancer in rural India.

BACKGROUND: Multimodality treatment of head and neck cancer in rural India is not always feasible due to lack of infrastructure and logistics. AIM: To demonstrate the feasibility of multimodality treatment for head and neck cancer in a community setting in rural India. SETTING AND DESIGN: Community cancer center, retrospective review. MATERIALS AND METHODS: This article focuses on practice environment in a cancer clinic in rural India. We evaluated patient profile, treatment protocols, infrastructure availability, factors impacting treatment decisions, cost estimations, completion of treatment, and major treatment-related complications for the patient population treated in our clinic for a 2-year period. RESULTS: A total of 230 head and neck cancer patients were treated with curative intent. Infrastructure support included basic operating room facility (cautery machine, suction, drill system, microscope, and anesthesia machine without ventilator support), blood bank, histopathology laboratory, and computerized tomography machine. Radiation therapy (RT) facility was available in a nearby city, about 75 km away. One hundred and fifty-four (67%) patients presented at an advanced stage, with 138 (60%) receiving multimodality treatment. One hundred and eighty-four (80%) patients underwent primary surgery and 167 (73%) received radiotherapy. Two hundred and twelve (92%) patients completed the treatment, 60 (26%) were lost to follow-up at 18-month median follow-up (range 12-26 months), with 112 patients (66%) being alive, disease free. Totally 142 were major head neck surgeries with 25 free flap reconstructions and 41 regional flaps. There were 15 (6%) major post-op complications and two perioperative mortalities. Average cost of treatment for single modality treatment was approximately 40,000 INR and for multimodality treatment was 80,000 INR. CONCLUSIONS: This study demonstrates that it is feasible to provide basic multimodality treatment to head and neck cancer patients in the community.

A retrospective evaluation of submandibular gland involvement in oral cavity cancers: a case for gland preservation.

The key factor mitigating against prognosis in head and neck cancer is nodal metastasis and its management. Neck dissection has been known to play an integral part in this type of cancer management. Submandibular gland preservation during neck dissection and post radiotherapy, have been known to improve subjective symptoms of xerostomia. The authors retrospectively surveyed the involvement of submandibular gland involvement in oral cancer with a view to confirm oncologic safety of submandibular gland preservation, as a first step in a quest to manage radiation induced xerostomia by submandibular gland transfer. The medical and pathological records of oral cancer patients who underwent surgical treatment at the authors' centre were reviewed retrospectively. 194 patients were included in the study. 229 submandibular glands were excised from the same number of neck dissections. 3 (1.3%) submandibular glands were involved with malignancies microscopically. The mode of involvement was by direct infiltration. In conclusion, no metastasis to submandibular gland was observed. This may suggest the oncologic safety of submandibular gland preservation and transfer.

Feasibility of organ-preservation strategies in head and neck cancer in developing countries.

BACKGROUND: Chemoradiotherapy is an established strategy for organ preservation in head-neck cancer. These protocols are associated with added toxicity and need support infrastructure. Practice setup and availability of resources vary at the community level in developing countries. AIM: To evaluate the feasibility of organ-preservation strategies in different settings in developing countries. SETTINGS AND DESIGN: Survey. MATERIALS AND METHODS: In a questionnaire-based study, questions were directed to clinicians with varied practice setups to gather information regarding infrastructure, finance, and feasibility of organ-preservation protocols and their current practice trends. STATISTICAL ANALYSIS: Descriptive. RESULTS: Responses from 100 clinicians with focused practice in head-neck oncology were analyzed. Sixty-one percent clinicians were practicing organ preservation for advanced head-neck cancers in their practice. However, 65% centers lacked sufficient infrastructure to support organ-preservation protocols. Forty percent patients were treated on cobalt-radiotherapy machine. Fifty-nine percent of clinicians suggested that less than third of their patients were fit to undergo chemoradiation and 67% believed that adherence to treatment protocol was observed in less than two-thirds of cases. Based on their experience 82% clinicians felt that only one-third patients requiring salvage would actually undergo treatment. The majority of the patients (68%) used personal funds for treatment and less than one-third of the patients could afford complete treatment. CONCLUSIONS: The infrastructure needed to support organ-preservation protocols varies significantly between centers in developing countries. It may not be feasible to perform organ-preservation strategies in certain centers and feasibility guidelines should be made for their judicious use in developing countries.

Head and neck cancer in India: need to formulate uniform national treatment guideline?

BACKGROUND: In a large and diverse country like India, there is a wide variation in the availability of infrastructure and expertise to treat head-neck cancer patients. Lack of consistent adherence to evidence-based management is the biggest problem. AIMS: There is an unmet need to evaluate the existing treatment practices to form the basis for development of effective and uniform treatment policies. SETTINGS AND DESIGNS: Prospective case series. MATERIALS AND METHODS: A group of previously treated, potentially curable patients presenting to our institution (from April 2009 to March 2011) were evaluated for appropriateness of initial treatment based on National Comprehensive Cancer Network or Tata Memorial Hospital guidelines. Data regarding treatment center, protocol and accuracy of delivered treatment and their eventual outcome were analyzed. STATISTICAL ANALYSIS: Descriptive. RESULTS: Amongst 450 newly registered patients, 77(17%) were previously treated with curative intent and 69(89%) of them were inappropriately treated. Seventeen (25%) patients were treated in clinics while 12(17%) in cancer centers and 34(50%) in corporate hospitals. Fourteen (20%) patients received chemotherapy, 22(32%) received radiotherapy and 14(20%) underwent surgery while 19(28%) patients received multimodality treatment. Disease stage changed to more advanced stage in 40(58%) patients and curative intent treatment could be offered only to 33(48%) patients. Amongst 56 patients available for outcome review, 18(32%) patients were alive disease-free, 20(36%) had died and 18(32%) were alive with disease. CONCLUSION: Large numbers of potentially curable patients are inappropriately treated and their outcome is significantly affected. Many initiatives have been taken in the existing National Cancer Control Program but formulation of a uniform national treatment guideline should be prioritized.

A meta-analysis comparing the safety and efficacy of azithromycin over the alternate drugs used for treatment of uncomplicated enteric fever.

BACKGROUND: Drug-resistant typhoid fever is a major clinical problem globally. Emergence of multidrug-resistant (MDR) S. Typhi has complicated therapy by limiting treatment options. OBJECTIVES: A meta-analysis was planned to determine the strength of evidence supporting use of azithromycin over the alternate drugs available for treatment of uncomplicated typhoid fever. MATERIALS AND METHODS: Studies were identified using electronic database such as MEDLINE and other data at the National Library of Medicine assessed using PUBMED search engine as well as Cochrane Clinical Trial Register. Randomized control trials (RCTs) comparing azithromycin with chloramphenicol, fluoroquinolones and cephalosporins in culture-proven enteric fever were included. Data was extracted and methodological quality was assessed. Risk ratio (RR) with 95% confidence intervals was estimated for the dichotomous outcomes and mean difference (MD) with 95% confidence was estimated for continuous data. Primary outcomes studied were clinical failure (CF), microbiological failure, and relapse. RESULTS: A total of seven RCTs involving 773 patients met with our inclusion criteria. In comparison to older fluoroquinolones, azithromycin is marginally better in reducing the chance of CF with RR 0.46 (95% CI 0.25-0.82), while in comparison to ceftriaxone, it significantly reduced the chance of relapse with RR 0.1 (95% CI 0.01- 0.76). There were no serious adverse events reported in any of the trials. CONCLUSION: Azithromycin can be recommended as a second-line drug in MDR typhoid fever, however, large trials involving pediatric age group patients are recommended to arrive at a definite conclusion.

Pectoralis major flap for head and neck reconstruction in era of free flaps.

The aim of this study was to evaluate factors affecting the selection of pectoralis major flap in the era of free tissue reconstruction for post ablative head and neck defects and flap associated complications. The records of patients who underwent various reconstructive procedures between July 2009 and December 2010 were retrospectively analysed. 147 reconstructive procedures including 79 free flaps and 58 pectoralis major flaps were performed. Pectoralis major flap was selected for reconstruction in 21 patients (36%) due to resource constrains, in 12 (20%) patients for associated medical comorbidities, in 11 (19%) undergoing extended/salvage neck dissections, and in 5 patients with vessel depleted neck and free flap failure salvage surgery. None of the flaps was lost, 41% of patients had flap related complications. Most complications were self-limiting and were managed conservatively. Data from this study suggest that pectoralis major flap is a reliable option for head and neck reconstruction and has a major role even in this era of free flaps. The selection of pectoralis major flap over free flap was influenced by patient factors in most cases. Resource constraints remain a major deciding factor in a developing country setting.

Origin of excess low-energy states in a disordered superconductor in a Zeeman field.

Tunneling density of states measurements of disordered superconducting Al films in high Zeeman fields reveal a significant population of subgap states which cannot be explained by standard BCS theory. We provide a natural explanation of these excess states in terms of a novel disordered Larkin-Ovchinnikov phase that occurs near the spin-paramagnetic transition at the Chandrasekhar-Clogston critical field. The disordered Larkin-Ovchinnikov superconductor is characterized by a pairing amplitude that changes sign at domain walls. These domain walls carry magnetization and support Andreev bound states that lead to distinct spectral signatures at low energy.

A meta-analysis of low-dose aspirin for prevention of preeclampsia.

BACKGROUND: Low-dose aspirin (LDA) is widely used for prevention of preeclampsia. However, conflicting results have been obtained from various studies. AIM: The aim of our study was to evaluate the effect of LDA in prevention of preeclampsia in high-risk and low-risk women. MATERIALS AND METHODS: A total of 19 randomized control trials were identified using PUBMED search engine and Cochrane Clinical Trial register. The study population was divided into high-risk and low-risk groups. The effect measured was incidence of preeclampsia in women taking either LDA or placebo where the relative risk (RR) and the 95% confidence interval (CI) were calculated for both groups. RESULTS: A total of 28237 women were studied, out of which 16550 were in the low-risk group while 11687 were in the high-risk group. The overall incidence of preeclampsia was 7.4%. With the aspirin group it was 6.9% while in the placebo group it was 7.8%. In the high-risk group there was 21% reduction in the risk of preeclampsia associated with the use of aspirin (RR 0.79, 95% CI 0.65-0.97). However, LDA is not effective in reducing the risk in low-risk population (RR 0.86, 95% CI 0.64-1.17). CONCLUSION: LDA has a small effect in the prevention of preeclampsia in women considered to be at high risk for the disease. However, it is not effective in reducing the risk in the low-risk group.