Progress in non-viral localized delivery of siRNA therapeutics for pulmonary diseases

Emerging therapies based on localized delivery of siRNA to lungs have opened up exciting possibilities for treatment of different lung diseases. Localized delivery of siRNA to lungs has shown to result in severalfold higher lung accumulation than systemic route, while minimizing non-specific distribution in other organs. However, to date, only 2 clinical trials have explored localized delivery of siRNA for pulmonary diseases. Here we systematically reviewed recent advances in the field of pulmonary delivery of siRNA using non-viral approaches. We firstly introduce the routes of local administration and analyze the anatomical and physiological barriers towards effective local delivery of siRNA in lungs. We then discuss current progress in pulmonary delivery of siRNA for respiratory tract infections, chronic obstructive pulmonary diseases, acute lung injury, and lung cancer, list outstanding questions, and highlight directions for future research. We expect this review to provide a comprehensive understanding of current advances in pulmonary delivery of siRNA.

Building capacities for universal health care in the Philippines: Development and implementation of a leadership training program for public health nurses

@#Achievement of Universal Health Care (UHC) in the Philippines requires capable health workers who can navigate changes and lead in the local implementation of health system reforms. Public health nurses are in a strategic position to lead in UHC implementation as they constitute the largest cadre of health workers in the public health setting, and core concepts of UHC intersect with principles of public health nursing practice. This paper aims to describe the development and implementation of a leadership training program for public health nurses in the Philippines, in response to UHC. Document reviews of training reports and evaluations, including course site data analytics, and evaluation of the training program were done for the four cohorts of the course. The University of the Philippines Manila College of Nursing, with support from the Department of Health, responded to the increased demand of the Philippine health system for public health nurses with strong foundations and advanced skills by designing and offering a leadership development course specific to PHNs. From November 2019 to March 2022, a total of 183 participants from 17 regions completed the training. With the COVID-19 pandemic and dynamic changes in governance, the experiences of the project highlighted the need for flexibility in delivering the training program, updating module contents according to the latest developments, and improving course duration and evaluation. Barriers to course engagement and completion must be addressed for PHNs, their workplaces, clients, and the health system to benefit the most from the training.

Primary versus revision total shoulder arthroplasty: comparing relative value and reimbursement trends

Total shoulder arthroplasty (TSA) has been demonstrated to be an effective treatment for multiple shoulder pathologies. The purpose of our study was to compare the relative value units (RVUs) per minute of surgical time for primary and revision TSA. Methods: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients that underwent primary TSA, one-component revision TSA, and two-component revision TSA between January 1, 2015 and December 31, 2017 using current procedure terminology codes. RVUs were divided by mean operative time for each procedure to determine the amount of revenue generated per minute. Rates were compared between the groups using a one-way analysis of variance with post-hoc Tukey test. Statistical significance was set at p<0.05. Results: When dividing compensation by surgical time, we found that two-component revision generated more compensation per minute compared to primary TSA (0.284±0.114 vs. 0.239±0.278 RVU per minute or $10.25±$4.11 vs. $8.64±$10.05 per minute, respectively; p=0.001). Conclusions: The relative value of revision TSA procedures is weighted to account for the increased technical challenges and time associated with these procedures. This study confirms that reimbursement is higher for revision TSA compared to primary TSA.

Formulations of desensitizing toothpastes for dentin hypersensitivity: a scoping review

Abstract Objective: This study aimed to review evidence from randomized controlled trials (RCTs) to describe: 1) the active ingredients and desensitizing toothpaste brands; 2) the evaluation of these active ingredients over time, and 3) the fluoride and abrasive content in the formulations designed to treat dentin hypersensitivity (DH). Methodology: In total, 138 RCTs and their tested toothpastes were included. Searches were updated up to August 19, 2021. Formulations, reported brands, active ingredients over time, and type of fluoride (ionizable or ionic fluoride) and abrasive (calcium or silica-based) were analyzed (PROSPERO #CRD42018086815). Results: Our trials assessed 368 toothpaste formulations, including 34 placebo (9%), 98 control toothpastes with fluoride (27%), and 236 (64%) with active ingredients to treat DH. We tested the following active ingredients: potassium compounds (n=68, 19%), calcium sodium phosphosilicate (CSP) (n=37, 10%), strontium compounds (n=28, 8%), arginine (n=29, 8%), stannous fluoride (SnF2) (n=21, 6%), hydroxyapatite (n=9, 2%), potassium combined with another active ingredient (n=19, 5%), inorganic salt compounds (n=11, 3%), citrate (n=5, 1%), formaldehyde (n=3, 1%), herbal (n=4, 1%), copolymer (n=1, 0.5%), and trichlorophosphate (TCP) (n=1, 0.5%). The number of toothpaste formulations increased since 1968, with the greatest increment after 2010. Most toothpastes described their type of fluoride as sodium monofluorphosphate (MFP) (n=105, 29%) and NaF (n=82, 22%), with silica-based (n=84, 23%) and calcium-based (n=64, 17%) abrasives. Conclusion: Patients and dentists enjoy an increasing number of brands and active ingredients to decide what desensitizing toothpaste to use. The most common types of fluoride are MFP and NaF.

Is Our Child Safe on the Escalator?

@#Introduction: This study aimed to explore the behaviour of Malaysian children aged 5 and less when traveling on the escalator. Methods: An observational study was conducted at six randomly selected shopping malls in the Kinta District of Perak State in Malaysia. Sample size of 258 caregiver-child pairs was calculated. Children and their caregivers were observed for unsafe behaviours by using a checklist consisting of 15 unsafe behaviours (e.g.: child sitting on escalator, travelling facing opposite direction, playing with the emergency stop button, not following caregivers’ instruction). The checklist was constructed from accredited escalator guidelines adapted from five different countries. A child was considered unsafe if there was at least one of the unsafe events observed. The proportion of child using escalator in an unsafe manner was analysed using IBM® SPSS® Statistics. Results: Of the 258 child-caregiver pairs observed, 149 (57.8%) children and 162 (63.8%) caregivers demonstrated at least one unsafe behaviour when using the escalator. ‘Not following caregiver’s instructions’ (28.7%) was the most common unsafe behaviour among children while the most common unsafe behaviour among caregivers was ‘not holding their child’s hand when using the escalator’ (41.7%). Four children used the escalator unattended. Conclusion: More than half of the children and their caregivers had used escalators in an unsafe manner and this required attention from the Public Health Department and the Department of Occupational Safety and Health to prevent unwanted injuries, especially among children.

Caring and witnessing in an urban poor community through engaged ethnography amidst the COVID19 pandemic

@#In this paper, I reflect on caring and witnessing through engaged ethnography of an urban poor community during the onset of the COVID19 pandemic. The urban poor are individuals and families who live below the poverty line in metropolitan areas, many of whom have little or no political voice and are insufficiently protected by social networks and other institutions. In March 2020, the government placed Metro Manila under Enhanced Community Quarantine to control the spread of COVID19. This left many an urban poor community in Metro Manila to struggle even more against an already precarious existence. By standard, nurses render different levels of care for urban poor clients in almost all health care settings. In public health nursing, we come in close contact to the realities of our clients when we see them in health centers, in the community, or whenever we do our home visits. Now, caring for vulnerable and marginalized groups such as the urban poor has changed due to minimum public health standards of wearing masks, physical distancing, handwashing, and enforcement of lockdowns. As a nurse, an academic, and as a student of anthropology, I came up for self-review while doing an article for a popular social news network derived from a virtually engaged ethnography. While this novel method requires you to see the world through the eyes of the “other,” and generates bioethical dialogue and awareness of personal biases in addressing ethical considerations and challenges, it gives voice and fulfills our roles as client advocates. In May 2020, the article was published with the urban poor organization and its partners as my coauthors. I borrowed from anthropology to arrive at a greater understanding of the socio-cultural effects and political implications of COVID19 to one of the most vulnerable nursing clientele – the urban poor.

Major Predisposing Factors Influencing the Suicide by Hanging: A Retrospective Study from a Tertiary Care Government Hospital in Kerala State, South India

Introdcution: A variable incidence of hanging is found assecond major group among the total number of autopsiesdone in the Department of Forensic Medicine, Govt. MedicalCollege, Calicut, Kerala state, South India. The incidences arefound to be varying according to the social and economic statusof the society. This retrospective study was done in a tertiarycare Government Hospital to find the major predisposingfactors influencing the suicide by hanging.Material and Methods: Case history were taken in detailfrom questionnaires to the relations of the deceased and fromPolice. The results were analyzed on the basis of history,postmortem findings and results of laboratory investigations.Results: The age group 16-25 was found to be the mostprevalent (75%) for suicidal hanging. Among the religion,Hindu religion showed the highest (80%) number. Morecases were found among the manual labourers and lowermiddle class people. People without children were moreprone to suicide by hanging. Among the precipitating factors,mental illness was the highest factor. Fracture of hyoid bonewas found during autopsy in majority of cases of completehanging.Conclusion: Psychological upset and educational statusplayed an important role in suicidal hanging. The highestincidence was seen among those with lower educational status.Hence, proper identification of such people and presentingthem to effective counselling may reduce the incident rate.

Normalizing advanced practice in public health nursing in The Philippines: A foucauldian analysis

@#<p style="text-align: justify;">This study provides a closer look to the possibility of having advanced practice in public health nursing by analyzing the power relations between nursing practice and social structures. Representatives from the public health sector, national authorities, and the private sector were invited in a round table discussion. Transcriptions were coded and later on categorized and analyzed drawing upon the concepts of Foucault. Foucauldian analysis hands an important insight on how social structures and institutions can steer the creation of an advanced practice in public health nursing in the Philippines. Various social institutions view the relevance of a master's prepared nurse according to their societal roles and functions. Requisite competencies of a master's prepared nurse in public health nursing include fulfilling the role of a clinician, leader and manager, supervisor, and a researcher. PRBON, CHED, DOH, and nursing schools need to work together to define the knowledge of an advanced practice in public health nursing, to implement appropriate surveillance mechanisms, and to establish a compliant practice.</p>

Evaluation of the Antimicrobial Effect of Carboxymethyl Cellulose versus Silver with Saline Dressing in Diabetic Ulcers.

Background: The diabetic foot ulcer is a major complication of diabetes mellitus. (1) It occurs in 15% of all patients with diabetes and precedes 84% of all lower leg amputations. (2) Diabetes mellitus impedes wound healing by prolonging the inflammatory phase. Increased glucose in the tissue precipitates infection. (3) Diabetic microangiopathy which affects microcirculation. Increased glycosylated hemoglobin decreases the oxygen dissociation. Increased glycosylated tissue protein decreases the oxygen utilization. This study is intended to show the efficacy of carboxymethyl cellulose (CMC) dressing for a faster healing of diabetic ulcers when compared with the conventional saline dressing. Materials and Methods: This study was a prospective case–control comparative study conducted at the Department of General Surgery and Gastroenterology, father Muller Medical College, Mangalore, from August to July 2016. 80 consenting patients who met the predefined criteria were taken for the study and divided into two groups, 40 patients each is put in the CMC with silver dressing group and the conventional saline dressing group. Results: There was no statistically significant difference between the two groups in terms of gender, age, glycemic control, and site of ulcer P < 0.001. In our study, we found that there was statistically significant difference in the rate of infection between the two groups. Conclusion: Silver impregnate dressings have a role in the management of diabetic ulcers by reducing the local burden of infection which is an important cause for non-healing ulcer analgesia.

Prevalence of dental caries and treatment needs among school going children of Chandigarh.

Introduction: Dental caries is the most common chronic disease of childhood that interferes with normal nutrition intake, speech, and daily routine activities. Dental caries is a lifetime disease, and the highest priority risk group is school children. Aim: To assess the prevalence of dental caries and treatment needs among school going children of Chandigarh. Materials and Methods: A cross-sectional study was done among school going children of Chandigarh in the age group of 3-17 years. The subjects were selected from four randomly selected schools. All the children from the selected schools were examined. A total of 4493 subjects formed the sample size. Dentition status was assessed using dft index by Gruebbel for primary dentition and DMFT index by Klein, Palmer, Knutson for permanent dentition, respectively. Chi-square test was used to find an association between the study variables. Independent t-test and one-way ANOVA were used to compare the mean difference. Results: Among the 4493 study subjects, caries prevalence was found to be 47.3%. Mean dft and DMFT score of the population was 1.06 ± 1.995 and 0.41 ± 1.022, respectively. When analyzing the treatment needs among various age groups 42.6% of the study subjects required oral prophylaxis and 45% required restorative procedures. Conclusion: Based on the findings, it can be concluded that high prevalence of caries was found in primary dentition than permanent dentition and most of the decayed teeth were untreated. This study emphasize the need for treating dental caries at its earliest possible stage and parents should be made aware of caries preventive measures for their children.

Physiological Variables, Psychosocial Factors and Age at Menarche Among Punjabi Girls.

The term menarche signifying the onset of menstruation is merely one manifestation of puberty. The age at menarche has been getting earlier all over the world with varying rates. An average decline of about 4 months per decade has been reported from the United States and in Western Europe over the period 1830–1960, while that in Eastern Europe since the late nineteenth century. There have been reports that there is a fairly good correlation between the age of menarche of mothers’ and their daughters’ (1, 2). The objective of this study was to find out the present age at menarche among Punjabi girls and correlate it with relevant variables. The age at menarche in the present study has been found to be significantly less as compared to data from the same region (Punjab, India). The decline in the mean age at menarche between the mothers and the daughters was statistically highly significant. There was a positive correlation between menarche and weight, height, triceps skinfold thickness, body mass index and maternal age at menarche. No significant correlation was obtained between menarche and income class and a negative correlation was obtained between menarche and birth order.

Assessment of periodontal status among dental fluorosis subjects using community periodontal index of treatment needs.

Aim: To determine the periodontal status and treatment needs among dental fluorosis subjects residing in Ennore, Chennai, using Community Periodontal Index of Treatment Needs (CPITN). Materials and Methods: All the subjects with dental fluorosis above 15 years of age, permanent residents of Ennore, were included in the study. Subjects with known systemic diseases and subjects with other intrinsic dental stains were excluded from the study. Periodontal status was estimated using CPITN and Dental fluorosis was recorded using Dean's Dental Fluorosis Index. Results: The total number of study subjects was 1075, of which 489 were males and 586 were females. Males were predominantly affected with periodontal disease than females. This was found to be statistically significant (P=0.000). The association between Degree of Fluorosis and Periodontal Status is statistically significant (P=0.000). There was statistically significant difference in mean number of sextants between the degree of fluorosis in each of the periodontal status (P=0.000). Conclusion: The finding that the lower prevalence of shallow pockets in the study area, where the fluoride level in the drinking water ranges from 1.83 to 2.01 ppm, indicates that the use of fluoride in water is beneficial to the periodontal tissues.

Prevalence of permanent tooth loss among children and adults in a suburban area of Chennai.

Aim: To determine the prevalence of permanent tooth loss among children and adults in a suburban area of Chennai. Design: Cross sectional descriptive study. Study setting: The study was conducted in Tiruverkadu, a suburban area of Chennai. Materials and Methods: A house-to-house survey was done in Tiruverkadu. The study population consisted of 6, 12, 15 years children, 35-44 years, and 65-74 years adults. Type III dental examination was carried out. Cross tabulations and Chi-square statistics were computed. The level of significance was chosen as P<0.05. Results: Out of the total 679 subjects, 309 subjects had tooth loss. Females (47.9%) had greater tooth loss compared to males (42.9%). Tooth loss increased as age progressed. Subjects in the lower socio-economic status had greatest tooth loss. The mean tooth loss among the subjects was 2.7. Conclusion: This study indicates that tooth loss increases with age and differs for gender and socio-economic status. The prevalence of tooth loss among the subjects was found to be high in children as well as in adults. Therefore, dental professionals should utilize various measures available in preventive dentistry to minimize tooth loss.

Cost-benefit analysis of the newborn screening program of the Philippines

BACKGROUND: Newborn Screening (NBS) is a public health activity aimed at the early identification of infants who are affected by certain genetic/metabolic/infectious conditions. A cost analysis is critical for national implementation for integration as a public health program. OBJECTIVES: 1) To determine the incidence rates of congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), galactosemia (GAL), phenylketonuria (PKU) and glucose-6-phosphate dehydrogenase (G6PD) deficiency; and 2) To determine whether NBS is cost-beneficial for each disorder individually or in combination, from a societal perspective. STUDY DESIGN: Cross sectional survey and cost-benefit analysis. SUBJECTS AND METHODS: The study was conducted through a screening survey of the original 24 Metro Manila hospitals. Newborns were screened for CH, CAH, GAL, PKU and G6PD deficiency after the 24th hour of life. Those who screened positive underwent serum confirmatory testing. Using incidence rates from the screening survey, a population of 1.5 million, and different screening combinations, the costs for the detection and treatment of the five disorders were compared to the benefits projected from preventing the corresponding complications and consequent productivity losses. For economic evaluation, we compared sequential analysis of doing tandem/multiple testing for the different disorders vs a "do-nothing" alternative. Sensitivity analyses for different incidence and discount rates were conducted to test the strength of the conclusions. RESULTS: The incidences of the disorders with 95% confidence intervals are: CH is 1:3 235 (1:2 219 - 1:5 946); CAH is 1:7 455 (1:4 046 - 1: 14245); GAL is 1: 106 006 (1: 44 218-1:266 796); and G6PD deficiency is 1:167 (1:151 - 1: 186). Screened individually, CH and G6PD deficiency had net benefits of US$ 5.29 M and US$ 15.44 M, respectively. The other conditions yielded net costs when screened individually - CAH (US$ 2.61 M), GAL (US$ 0.90 M) and PKU (US$ 6.74 M). Pairing the disorders with CH showed the following benefit:cost ratios - CH + CAH, 1.3; CH + GAL, 2.0; CH + G6PD deficiency, 3.4; and CH + PKU, 0.9. Combining disorders resulted in the following benefit:cost ratios - CH + CAH + GAL, 1.2; CH + CAH + GAL + PKU, 0.8; and CH + CAH + GAL + G6PD deficiency, 2.1. Screening for the 5 disorders in tandem resulted in a benefit:cost ratio of 1.4 and a net benefit of US$ 11.42 M.

Efficacy and safety of three concentrations of levobupivacaine administered as a continuous epidural infusion for infusion for postoperative analgesia in Filipino patients undergoing lower extremity orthopedic surgery

Single enantiomer compounds like levobupivacaine appear to be safe alternative to racemic agents, like bupivacaine for postoperative analgesia. This double-blind randomized dose ranging trial amed to compafe the efficacy sna safety of three concentration of continuous epidural infusion of levobupivacaine for postoperative analgesia after lower extremity orthopedic surgery. After informed consent, 63 eligible patients were randomized to receive levobupivacaine 0.0625%, 0.125%, or 0.25% as a continuous postoperative epidural infusion. Intraoperatively,vital signs, oxygenation, sensory block level, motor block, and abnormal signs and symptoms were monitored. on and a half (1 1/2) hours after the last intraoperative bolus of levobupivacaine, the epidural infusion was started at a rate of 6/ mL/h for 24 24 hours. Pain intensity and pain reliefscores, using the 10-cm visul analog scale, were assessed postoperatively. The time to first request for analgesia (with morphine or tramadol) and the total rescue doses gicen were recorded. Twenty patients were randomized to Goup A (0.0625%), 22 to Group B (0.125%), and 21 to Group C (0.25%). All three group were similar as to age, gender distribution and baseline physical findings. Pain scores, pain relief, and ie to the first rescue does were not significant different among the three groups. The most common adverse events were fever (8%), hypotensy (3%), and vomiting (2%). one patient developed severe hypotensio probably secondary to inadequately replaced intraoperative blood loss. Levobupivacaine is effective and safe for postoperative analgesia as an epidural infusion at 0.0625%, 0.125%, and 0.25%.

Perforated Meckels diverticulum causing giant pseudocyst and secondary appendicitis.

Meckels diverticula are known to present with a myriad of complications. However its perforation followed by development of a giant pseudocyst and secondary appendicitis is not reported in literature thus far. We report this complication in a five and half month old infant.

Cost-benefit analysis of newborn screening for galactosemia in the Philippines.

To determine the incidence of galactosemia (GAL) in the Philippines and to determine whether newborn screening for GAL is cost-beneficial from a societal perspective, cost-benefit analysis was performed. Newborn screening for GAL was done after the 24th hour of life using the Beutler test. Patients screened positive were recalled for confirmatory testing. Using incidence rates obtained from the different participating hospitals of the Philippine Newborn Screening Program (PNSP), the costs for the detection and treatment of GAL were compared to the expected benefits by preventing mental retardation, cataracts and other physical disabilities caused by the disorder that would lead to a loss of productivity for the individual. Sensitivity analyses for incidence and discount rates were also included. Of the 157,186 newborns screened by the PNSP since its inception in 1996, 8 screened positive results. Confirmatory testing of these patients showed that 2 had galactosemia. The incidence of galactosemia in this population therefore, is 1 in 106,006 (95% CI= 1:44,218 - 1:266,796). Projecting the figures to the actual birth rate (1.5M newborns/year), the total costs of the screening program amounted to $1.1M, while the total benefits amounted only to $0.2M, yielding net cost of $0.9M. A cost-benefit analysis of the screening program for galactosemia using the incidence 1 in 106,006 demonstrated that the costs of the program outweigh the benefits. The true incidence of galactosemia in the Philippine population may yield an incidence rate that will result in greater net benefits for the program.