Development of Spectrophotometric Methods for the Determination of Nalbuphine Hydrochloride in Different Forms

Abstract

Spectrophotometric methods for the quantitative determination of Nalbuphine Hydrochloride (N-HCl) in different forms which are raw samples, pharmaceutical preparation form and biological samples (spiked urine samples) were established. The proposed methods found to be simple, rapid, sensitive, precise and accurate. The determination proposed methods based on the reaction between nalbuphine hydrochloride in its different forms with coloring reagents forming colored ion associates, the ion associates exhibit absorption maxima in visible region which can be used in determination the concentration of Nalbuphine Hydrochloride (N-HCl). The used coloring agents are Bromophenol Blue (BPB) and Chlorophenol red (CPR) reagents. The optimum reaction conditions for quantitative analysis were investigated. In addition, the molar absorptivity and Sandell sensitivity were determined for the Nalbuphine Hydrochloride (N-HCl). The ion associates exhibit absorption maxima at 410 and 400 nm of (N-HCl) with BPB and CPR respectively. (N-HCl) could be determined up to 137.5ug/mL and 50ug/mL, using BPB and CPR respectively.

The correlation coefficient was ≥0.998 (n=6) with a relative standard deviation (RSD) ≤0.74 for five selected concentrations of the reagents. Therefore the concentration of N-HCl in its pharmaceutical formulations and spiked urine samples had been determined successfully.

Keywords: Naluphine Hydrochloride; Bromophenol Blue; Chlorophenol red

Introduction

Nalbuphine hydrochloride (5a,6a)-17-(Cyclobutylmethyl)-4,5- epoxymorphinan-3,6,14-triol hydrochloride, is narcotic analgesic drug which is a morphine- like drug with agonist activity at the k- opioid receptor and antagonist activity at the μ-opioid receptor. Nalbuphine is recommended for use in moderate to serve pain and its indications include pain after myocardial infraction.

There are several published research’s relating to methods for estimating Naluphine Hydrochloride (N-HCl) quantitatively in their dosage forms including spectrophotometric method [1-3], liquid chromatography mass spectrometry LC/MS [4], High Performance Liquid Chromatogrphy HPLC [5-7], gas chromatography [8] gas chromatography mass spectrometry GCMS [9], ion selective electrode [10].

In the present work the ion associate complex of nalbuphine hydrochloride (in raw samples, dosage form and in spiked urine samples) were studied spectrophtometrically. The proposed methods found to be selective, simple, rapid, sensitive, precise and accurate.

Experimental

Apparatus

Spectrophotometric measurements of N –HCl (Figure 1) with BPB and CPR reagents were measured using Agilent 8543 UV-Vis spectrophotometer equipped with quartz cell of 1 Cm optical path length with a resolution of 0.1 nm. The pH measurements of the prepared solutions were adjusted using HI 2211 benchtop pH meter HANNA. All spectrophotometric measurements were carried out at room temperature (25±2oC). Moreover, Millipore distillation apparatus model Direct Q3, France used for supplied deionized water.

Conclusion

The proposed methods were made by using simple reagents, which most ordinary analytical laboratories can afford. The methods are sufficiently sensitive to permit determination of the investigated drugs at given optimum conditions in pure solutions, pharmaceutical preparations and spiked urine samples.

Unlike gas chromatography and high performance liquid chromatography, Spectrophotometry is relatively simple to handle and affordable.

The proposed methods are simple, precise, accurate, robust, rugged and low coast. Therefore, the proposed methods should be useful for routine quality control purposes and pharmaceutical industries.

MMP13 and SERPINB2 as Novel Biomarkers for Hypopharyngeal Cancer

Abstract

Matrix Metalloproteinase (MMP)13 and serine peptidase inhibitor, clade B, member 2 (SERPINB2) are important components of the extracellular matrix and play a regulatory role in tumor stromal remodeling. The purpose of the study is to evaluate the expression of MMP13 and SERPINB2 in hypopharyngeal cancer. We utilized the public datasets to find the differentially expressed genes of hypopharyngeal cancer, which were verified by immunohistochemistry. At the same time, the role of differential expressed genes in prognosis was explored. We found that MMP13 is upregulated and SERPINB2 is downregulated in public datasets. We confirmed this conclusion by immunohistochemistry of hypopharyngeal cancer tissues and found that MMP13 and SERPINB2 were related to some clinicopathological factors. Moreover, SERPINB2 is an independent prognostic factor for hypopharyngeal cancer patients. MMP13 and SERPINB2 may predict the early recurrence of hypopharyngeal cancer. MMP13 combined with SERPINB2 may be potential prognostic biomarkers and drug targets in hypopharyngeal cancer.

Keywords: Hypopharyngeal neoplasms; Matrix metalloproteinase 13; Plasminogen activator inhibitor 2; Immunohistochemistry

Abbreviations

AUC: Area Under ROC Curve; CI: Confidence Interval; DAB: 3, 3’-Diaminobenzidine tetrahydrochloride; DEGs: Differentially Expressed Genes; ECM: Extracellular Matrix; FC: Fold-Change; GEO: Gene Expression Omnibus; H&E: Hematoxylin and Eosin; H3K4me3: Histone H3 trimethylation at lysine 4; HR: Hazard Ratio; ING: Inhibitor of Growth; MMPs: Matrix Metalloproteinases; PAI: Plasminogen Activator Inhibitor; TCGA: The Cancer Genome Atlas; uPA: urokinase type Plasminogen Activator; WHO: World Health Organization

Introduction

As an uncommon malignant tumor, hypopharyngeal cancer accounts for 3–5% of head and neck tumors [1]. Most pathological types of hypopharyngeal cancer are squamous cell carcinoma. Due to the occult anatomical location of hypopharyngeal cancer and poor surgical effect, local recurrence or distant metastasis often occurs in patients with hypopharyngeal cancer following surgery. Pharyngeal fistula also affects the quality of life of hypopharyngeal cancer patients. Therefore, it is necessary to search forhypopharyngeal cancer markers.

Tumor stroma is mainly composed of collagen fibers, vascular vessels, and Extracellular Matrix (ECM) components. ECM components are over-deposited in tumor tissues and function in nourishing tumor cells. The system composed of urokinase type Plasminogen Activator (uPA), plasmin, Plasminogen Activator Inhibitor (PAI), and Matrix Metalloproteinases (MMPs) is one of the main ways to regulate ECM degradation. MMP13, also known as Collagenase 3, can degrade a variety of ECM components, including tenascin C, fibronectin, and type I–IV collagen [2]. MMP13 has a wide range of proteolytic functions, and MMP13 participates in various physiological and pathological processes [3]. SERPINB2, also known as PAI-2, is a member of the SERPIN superfamily of serine protease inhibitors. SERPINB2 mainly inhibits uPA and tissue plasminogen activator [4]. Previous studies have shown that MMP13 [5,6] or SERPINB2 [7,8] are associated with the occurrence or prognosis of different tumors. However, until now, there has been no report on the expression and regulation of MMP13 and SERPINB2 in hypopharyngeal cancer. As a rare tumor, hypopharyngeal cancer also lacks markers for diagnosis and prognosis.

This is the first study to investigate the expression and correlation of MMP13 and SERPINB2 in hypopharyngeal carcinoma. Through public datasets and immunohistochemistry, we showed the expression changes and correlations of MMP13 and SERPINB2 in hypopharyngeal cancer. MMP13 and SERPINB2 are related to the survival of hypopharyngeal carcinoma patients and may predict early recurrence. These findings suggest that MMP13 and SERPINB2 play an important role in hypopharyngeal cancer and may be a potential prognostic marker and therapeutic targets for patients with hypopharyngeal cancer.

Methods

Public datasets searching

From the National Center of Biotechnology Information Gene Expression Omnibus (GEO) database (https://www.ncbi. nlm.nih.gov/gds/), we searched raw gene expression data of the hypopharyngeal cancer as the following key terms: (hypopharyngeal or hypopharynx) and (cancer or tumor or carcinoma or neoplasm). The publication time was not limited. Homo sapiens was selected in the Organism and Expression profiling by array in the Type.

GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) is an online tool provided by GEO, which is based on the R language limma package [9]. GEO2R was used to screen DEGs (differentially expressed genes) between hypopharyngeal cancer and non-cancerous samples in the GEO datasets and we further visualized DEGs by volcano plot [10]. A P-value <0.05 and absolute log Fold-Change (FC) greater than 2 for the DEGs were used as the cut-off criteria. We also used the online tool Venny 2.1 (http://bioinfogp.cnb.csic.es/tools/venny/ index.html) to identify the overlapping DEGs that were up-/downregulated in the GEO datasets.

The Cancer Genome Atlas (TCGA) is a public funded project that aims to catalogue and discover major cancer-causing genomic alterations to create a comprehensive “atlas” of cancer genomic profiles. We also obtained gene expression data in hypopharyngeal and non-cancerous tissues from TCGA database (https://cancergenome. nih.gov/). Both GEO and TCGA datasets’ non-cancerous tissues came from keratinized epithelium of hypopharynx in healthy volunteers.

Patients and tissue samples

The research was in consent by the First Affiliated Hospital of China Medical University Ethics Committee. We involved patients who signed informed consent and collected samples according to the informed consent. We collected 40 hypopharyngeal cancer patients who underwent partial hypopharyngeal resection or total laryngectomy and collected their cancer and paracancerous tissues. Two independent pathologists examined all tissues. No distant metastasis or preoperative chemoradiotherapy was observed. Besides, we collected patients’ clinical information and followed up. Smokers ware defined as those who smoke continuously or accumulatively for six months or more in their lifetime [11], according to the World Health Organization (WHO) guideline.

Immunohistochemistry

Formalin-fixed tissues were embedded in paraffin and cut into 5 μm–thick sections for Hematoxylin and Eosin (H&E) staining and immunostaining. The expression of MMP13 and SERPINB2 was assessed by immunohistochemical staining kit (Maixin, China). Dewaxed sections were washed in PBS and exposed to 3% H2O2 for 15 min at room temperature to quench endogenous peroxidase activity. Then the tissues were blocked with normal goat serum for 20 min at room temperature. After incubation overnight at 4 °C with primary antibody (1:200) (MMP13: proteintech, 18165-1-AP; SERPINB2: proteintech, 16035-1-AP), the tissues were incubated with the second antibody and biotin-labeled horseradish peroxidase. Subsequently, the antibody binding was visualized with a 3,3’-Diaminobenzidine tetrahydrochloride (DAB) kit (Maixin, China) before brief counterstaining with hematoxylin. Eventually, tissues were gradually dehydrated, sealed with neutral gum, observed and photographed with an inverted phase contrast microscope.

Immunoreactivity was semi-quantitatively evaluated and evaluated by two pathologists. Five representative regions were randomly selected from the 400-fold field of view of the microscope. The score of each field of view was determined by the proportion of positive cells and the color rendering intensity. According to the proportion of positive cells: <5%, 5-25%, 25% – 50%, 50% – 75%, 75% – 100%, the scores of 0, 1, 2, 3 and 4 were obtained respectively. According to the intensity of colouring, 0, 1 and 2 points were obtained for uncolored, yellow and brown respectively. The final score was obtained by multiplying the scores of the two items and taking the average score of the five visual fields. The total score of 0-4 was defined as Low-No expression, and more than 4 was defined as Medium-High expression.

Statistical analysis

Each experiment was repeated at least three times and data was analyzed by SPSS 21.0 (IBM Corp.). The expression of MMP13 and SERPINB2 in cancer and non-cancerous groups was compared by Student’s t-test (public data: unpaired t-test; specimen data: paired t-test). Pearson’s X² correlation was applied to test the correlations between expression of MMP13 and SERPINB2. Univariate analysis (Kaplain-Meier test) was used to determine the clinicopathological characteristics related to survival, and multivariate analysis (Cox regression) was used to further analyze the covariates (P <0.05) in univariate analysis. Finally, the diagnostic value was evaluated by area under ROC curve (R package ggplot2). Differences were considered significant when p -values <0.05.

Results

Identification of Differentially Expressed Genes (DEGs)

The gene expression profiles of GEO datasets, including GSE686 (cancer samples: 9, non-cancerous samples: 3), GSE2379 (cancer samples: 14, non-cancerous samples: 4), and GSE10774 (cancer samples: 10, non-cancerous samples: 4) were downloaded from the public GEO database by searching the terms mentioned. DEGs in the GSE686 dataset were screened and we obtained 231 DEGs (36 upregulated and 172 downregulated), as shown in (Figure 1A). In the GSE2379 and GSE10774 datasets, we identified 403 (204 upregulated and 199 downregulated) and 99 (23 upregulated and 76 downregulated) DEGs, respectively (Figure 1B- C). Among the DEGs, we found two overlapped DEGs, one upregulated (MMP13) and one downregulated (SERPINB2) (Figure 2A-B).

Conclusion

Our study assessed the role of MMP13 and SERPINB2 in hypopharyngeal cancer. The results showed that MMP13 may be an oncogene while SERPINB2 may be an anti-oncogene and could serve as a prognostic and diagnostic factor for hypopharyngeal cancer patients. We believe MMP13 and SERPINB2 could be promising biomarkers and drug targets for HNSCC.

Level of Knowledge of the Human Papilloma Virus in Women of a Primary Care Unit in Tijuana B.C.

Level of Knowledge of the Human Papilloma Virus in Women of a Primary Care Unit in Tijuana B.C.

Abstract

Background: The prevalence of the Human Papillomavirus (HPV) in Mexico fluctuates between 10-12%. Due to the low knowledge about HPV, women do not perceive the risk and ignore the possible consequences of this sexually transmitted infection.

Aim: The purpose of this study is to determine the level of knowledge of the HPV in women of the Family Medicine Unit #27 (FMU 27) of Tijuana, Mexico.

Design and Setting: Analytic cross-sectional study.

Methods: An analytical cross-sectional study was carried out, the level of knowledge of Human Papilloma Virus was measured in women from FMU 27 during August-October 2019. Qualitative variables were expressed in frequencies and percentages; central tendency and dispersion measures were used for quantitative variables. Chi-square was used for the bivariate analysis, a p <0.05 was considered significant.

Results: 194 patients were analyzed, 41% had a free union, 47.9% had secondary education (p= 0.003), 69.1% were employed and 55.2% had a lower middle socioeconomic level (p= 0.003). Regarding the level of knowledge, 71.1% was high, 25.8% medium and 3.1% low.

Conclusion: A high level of knowledge about HPV was evidenced. We recommend continuing to implement educational programs at different ages to further increase awareness of this disease.

Keywords: Level of Knowledge; Human Papillomavirus

Introduction

The HPV is a virus that belongs to the papolomaviridae family [1]. It infects and replicates in the nucleus of epithelial cells, its main site of involvement is the transitional epithelium of the cervix, affecting basal cells of the squamous epithelium. It has the ability to infect on contact with the skin, by sexual and vertical transmission at the time of delivery. The benign manifestations are condyloma and genital warts produced by non-oncogenic genotypes 6 and 11 (HPV6, HPV11); oncogenic genotypes 16 and 18 (HPV16, HPV18) cause 70% of cervical cancer. The highest prevalence rates are observed in women under 25 years of age, with a significant decrease between 25- 40 years [2].

Cervical cancer is the second most common cancer in women [3]. In Mexico it constitutes one of the main public health problems, with an incidence of 15.5% and a mortality of 12.8%, although it occurs in developing countries, a common denominator is the scarce economic resource and the low educational level [4]. HPV penetrates the suprabasal cells of the cervical epithelium where by viral transcription and repression of its late genes L1 and L2, it infects the keratinocyte [5]. The beginning of an active sexual life and the first pregnancy at an early age, multiparity, illiteracy, low socioeconomic level, hormonal contraceptives, smoking, a diet low in antioxidants, HIV co-infection and no access to social security, are the risk factors most strongly associated with the development of cervical HPV-cancer [4-6].

The Department of Epidemiology of the Ministry of Health in Mexico has established that cervical cancer detection programs should focus on three factors: achieving 80% coverage in the screening of the target population; ensure diagnosis and offer adequate and timely treatment in women with abnormal results [7]. The screening method is cervical cytology (Papanicolaou), a primary tool for the detection of premalignant lesions [8]. There are two vaccines against HPV, the bivalent vaccine (Cervarix) that contains antigens for types 16 and 18; and the quadrivalent vaccine (Gardasil) with antigens for types 16, 18, 6 and 11. The schedule used in Mexico is 0-6-60 months, or a two-dose schedule (0-6 months/0-12 months) [9]. According to the World Health Organization (WHO), vaccination is recommended for girls between 9 and 13 years of age [10]. In the acceptability of vaccines, prior knowledge of the vaccine by parents could be the main determining factor for its application [11].

The level of knowledge about the human papillomavirus is defined as the result of the assimilation of information by a person about the virus that is transmitted through sex, which affects the genitalia of men and women [12]. It is important for the general population to know about HPV and related risk factors, which affect women’s health [13]. Therefore, the main objective of the research was to determine the level of knowledge of HPV in women from Tijuana.

Material and Methods

Study Design and Population

An analytical cross-sectional study was conducted between August-October 2019 at FMU 27 of the Instituto Mexicano del Seguro Social (IMSS). Women between 25-45 years old who agreed to participate in the study by informed consent were included. Patients with some mental disability or psychiatric illness were excluded from the study; patients with incomplete information were eliminated. A structured interview was conducted on a data collection form, which allowed obtaining personal, sociodemographic and clinical data.

Variables

The collection of variables was done with a standardized data form; the variables collected were age, marital status, education and occupation, which were asked directly; the knowledge about HPV was measured through the questionnaire “The Human Papilloma Virus and its health”, which has 16 questions, validated in Spanish with a Kuder-Richardson reliability coefficient of 0.76; this instrument classifies knowledge as low (0-5 points), medium (6-10 points) and high (11-16 points) [14]; finally, the socioeconomic level was obtained using the Graffar-Mendez Castellanos scale, a validated instrument in Spanish (Cronbach’s alpha 0.75), it measures four dimensions and classifies the family into 5 categories, upper class (4-6 points), high average (7-9 points), low average (10-12 points), worker (13-16 points) and marginal (17-20 points) [15,16].

Statistical Analysis

Descriptive statistics were performed; qualitative variables were expressed in frequencies and percentages; mean and standard deviation were used for quantitative variables. Chi-square was used for the bivariate analysis. The results were evaluated in a 95% confidence interval, a p <0.05 was considered significant. For data analysis, the IBM SPSS program, version 21 was used.

Ethics

The study was approved by the Local Committee of Ethics and Health Research number 204; with registration number R-2019-204- 022. The research was conducted under the General Health Law on Health Research, the Helsinki declaration and Bioethical principles. The participants signed the informed consent.

Results

194 women were analyzed, with a mean age of 33.98 ± 6.07 years. According to their marital status, 41% were in free union, 37% married, 16% single, 5% divorced and 1% widowed. In schooling, 47.9% had secondary school, 21.6% primary, 19.6% high school, 8.8% university and 2.1% lacked studies. The majority were employed (69.1%), 24.7% dedicated to the home, 5.6% merchants, and 0.5% pensioners; 55.2% had a lower middle socioeconomic level, 33% working class, 10.3% middle class, and only 1.5% marginal stratum. The level of knowledge of the human papillomavirus was high in 71.1%, 25.8% medium level and 3.1% low level (graphic 1).

Discussion and Conclusion

The most important finding of our research was a high level of knowledge among the study participants, a result much higher than the study by Medina-Fernandez et al., [13] who demonstrated a good level of knowledge in 22%, 20% regular, 18% deficient and 40% very deficient. Regarding the sociodemographic characteristics, similarities were found between the frequency of secondary schooling and that married women have greater knowledge of HPV. On the other hand, Hernandez-Marquez et al., [17] in Cuernavaca Mexico, identified that 57% of women showed a medium level of knowledge, 23% low and 20% high, of which 45% had a medium socioeconomic level, and 63% basic schooling; percentages below what was identified in our study with a low average socioeconomic level of 55% and 48% with basic education, these results indicate cultural, social and health differences between the regions of our country, for this reason we can demonstrate that the level of knowledge about HPV increases with schooling.

In the same study it was detected that a higher level of knowledge is related to the acceptance of the cervical cytology sample [17], for this reason it is essential to disseminate prevention strategies in a population with limited economic resources, and to establish mechanisms that help greater source of information on the prevention and detection of this disease through cervical cytology, because in Mexico we have a detection rates of 50% [18], much lower than the international indicator for screening (80%). In conclusion, our study shows a high level of knowledge about the human papillomavirus in women of FMU 27. Education is the key element for the prevention, detection and diagnosis of HPV infection [19]; we recommend carrying out and reinforcing dynamic educational programs that are easily adjusted to the needs of health institutions, aimed at the different age groups affected by this sexually transmitted infection. Therefore, it is necessary to carry out multicenter studies to compare the knowledge in different populations of the state of Baja California and Mexico.

Perspectives on Transitional Care for Vulnerable Older Patients: A Qualitative Study

Abstract

Background: Transitional care for vulnerable older patients after acute hospitalization back home is increasingly important. Despite previous studies, optimal transitional care of vulnerable older patients remains undefined.

Purpose: This study explores what is needed to satisfy these patients with transitional care, from the perspectives of these patients themselves, informal caregivers and nurses.

Methods: Patients (n=13) and informal caregivers (n=10) were interviewed after hospital discharge. Hospital and home care nurses (n=9) participated in two focus groups. Verbatim transcriptions were analyzed according to the framework method.

Results: Patients (mean age 85.5) and informal caregivers indicated transitional care is optimal if, on top of the organization of this transition, they have trust in the professionals involved. Elements of this organization and trust together stimulated three preferred outcomes of transitional care: the patient going home, the patient reaching adequate health and feeling safe. Nurses indicated no other elements or outcomes.

Conclusion: Transitional care for vulnerable older patients is optimal if, on top of the organization of transitional care, these patients and their informal caregivers have trust in the professionals involved. Regarding the challenge of organizing increasingly complex transitional care for vulnerable older patients, the focus should shift towards optimizing trust.

Keywords: Discharge Planning; Nurse-Patient Relationships; Older Adults; Patient Perspectives; Primary/Secondary Care Interface

Background and Purpose

The population of older persons is growing and the length of hospital stays decreased over the last decades. These trends together cause a rapid increase in the number of older patients experiencing hospital discharge while still being in a vulnerable status . For these patients, rehabilitation for a larger part takes place outside the hospital, under the responsibility of primary care providers . Besides, the proportion of Dutch older persons receiving primary care by home care organizations has increased . Hence, transitional care, the continuity of care between the inpatient hospital care and primary care back home, is increasingly important for vulnerable older patients.

In reaction to these trends, many interventions have been developed to optimize transitional care for vulnerable older patients over the last decades. Among others, interventions were developed that implemented communication between hospital and primary care providers before hospital discharge , discharge planning , geriatric assessments and post discharge support into organizational structures. Many of these interventions aim to reduce length of hospital stays, number of ED visits after discharge or to improve quality of life. Reviews showed that several of these interventions indeed do so . However, the underlying mechanism improving these outcomes remained unknown .

Accordingly, patients’ experiences with transitional care often remain suboptimal . Little is still known about what is needed to optimize transitional care from the perspectives of vulnerable older patients . Until today the majority of qualitative studies regarding transitional care for vulnerable older patients focused on the perspectives of professional care providers. However, their perspectives are divergent . Exploring the perspectives of vulnerable older patients on transitional care and comparing their perspectives to the perspectives of health care providers may help to point further research, health care innovations and policy development on optimizing transitional care in the right direction.

Methods and Procedures

Design

This study has a qualitative design using semi-structured interviews and focus groups. We conducted interviews with vulnerable patients aged 70 years old and over, who were recently discharged after acute hospitalization with an indication for home care, and their informal caregivers. Elements of optimal transitional care were identified from their perspectives. Focus groups were conducted with hospital and home care nurses to explore major differences and similarities between the perspective of these professionals and the perspective of vulnerable older patients and their informal caregivers. The interviews and focus groups were performed between April and November 2017 in the South Holland province of the Netherlands. Participants were recruited from an academic hospital, a regional hospital and several home care organizations.

Participants

Vulnerable older patients were selected from the hospitals’ electronic patient files by entitled geriatric and transfer nurses in March 2017. Inclusion criteria were age of 70 years old or over, acute hospitalization and vulnerability during the hospital stay according to the Dutch ‘VMS screening’ that regards age, delirium, falling, malnutrition and physical limitations. Exclusion criteria were terminal illnesses, language barriers and living outside the study area. Eligible patients were contacted by telephone to ask for their participation in an interview at home about their experiences around their hospital discharge, preferably together with one of their informal caregivers. The aim was to recruit approximately fifteen patients to be able to reach data saturation.

To invite hospital and home care nurses for participation in a focus group, an e-mail was sent to care managers of the four largest home care organizations in the area and to the heads of three hospital departments per hospital. The aim was to organize two focus groups in which various home care organizations and the two hospitals would be represented. There were no exclusion criteria.

All participants gave oral and written informed consent before the start of their interview or focus group. The area’s medical ethical committee ‘CME’ did not need to approve upon the study, since the study was not subject to the Dutch Medical Research Involving Human Subjects Act (WMO).

Data Collection

The semi-structured interviews were guided by topic lists. To compose this topic list, we selected questions possibly relevant to vulnerable older patients and their informal caregivers in transitional care from four well known Dutch and European existing questionnaires on continuity of care, hospital care, preoperative care and general practice care , and from a topic list of an earlier qualitative study about elderly persons’ experiences with participation in hospital discharge process . The topic list was checked by members of a regional older person’s advisory board and a pilot interview was performed. The topic list included questions about continuity of care, alignment, information provision, patient participation, interaction with professional care providers, feelings, overall satisfaction, points for improvement and demographic characteristics. All interviews took place at the patients’ homes and were performed by a master student.

For the semi-structured focus groups, a topic list was written as well. The main question of this topic list was ‘What is the ideal transition of care for vulnerable older patients?’. Other questions were about the organization, barriers, improvements, target group, tips and tops of transitional care for vulnerable older patients and demographic characteristics. Focus groups took place in the academic hospital within the study area and were moderated by a junior researcher and observed by a senior researcher. All interviews and focus groups were audio recorded and field notes were made.

Qualitative Analysis

The audio recordings were transcribed verbatim. For familiarization with the data, all audio recordings were listened. Analyses were performed by two researchers according to the framework analysis as described by Green and Thorogood. in Microsoft Office Word and Excel as follows. Based on elements of optimal transitional care identified from openly coding the focus group transcripts and two interview transcripts and from literature, a framework of codes was made. Subsequently, all transcripts were coded with this framework. New codes and sub-codes were added throughout the coding process. Some codes were grouped into plausible elements of transitional care according to the researchers. By re-reading and re-coding, elements were organized into a conceptual model about which consensus was reached between the researchers. Participants’ demographic characteristics were described by making use of IBM SPSS Statistics version 23 descriptive statistics.

Results

Of the selected 25 patients eligible for participation, 6 were excluded because of terminal illness (n=2), language barriers (n=3) or living outside the region (n=1). Of the 19 vulnerable older patients approached, thirteen (68%) agreed upon participation in an interview. All interviews took place seven to thirteen days after hospital discharge and lasted for 25 minutes to one hour. In Table 1 the characteristics of the participants from the interviews and the focus groups are presented. The patients’ mean age was 85.5 years old (SD 1.5, range 77 to 95), 8 of them (61.5%) of them were female and their hospital stay ranged from 3 to 14 days (mean 8.0 days (SD 1.0)). In 10 of the 13 executed interviews, an informal caregiver participated as well. The informal caregivers of two patients had work obligations at the moment of the interview and one patient did not have any informal caregivers. The informal caregivers were spouse (n=3) or offspring (n=7) of the patient. Interviewed patients and informal caregivers graded their satisfaction with the transition of care in a range from 6 to 10 on a 0-10 scale (patients: mean 8.1 (SD: 0.3), informal caregivers: mean 7.8 (SD 0.5)). Data saturation was reached.

Table 1: Baseline characteristics.

The 10 nurses who signed up to participate were divided over two focus groups. 9 of them (90%) showed up. In total, 5 of them were hospital nurses and 4 were home care nurses. They represented an academic hospital, a regional hospital and three home care organizations in the study area. Both focus groups lasted approximately 75 minutes.

Perspectives of Patients

Patients and informal caregivers indicated what Informal Caregivers elements of the transition of care contributed to the quality of this care for vulnerable older patients. Some of these elements had to do with the underlying need for ‘organization’ of the transition and some with the underlying need ‘trust’ in professionals. Both organization and trust contributed to three preferred outcomes vulnerable older patients and their informal caregivers have in the transition of care: going home, adequate health and feeling safe.

Preferred Outcomes

The most prominent preferred outcome of vulnerable older patients and informal caregivers in transitional care was ‘the patient going home’ (quote 1). A second preferred outcome was both the patient and informal caregiver feeling safe. The third preferred outcome was the patient reaching an adequate health status, which was specified as recovery, as reaching independency or as prevention of rehospitalization. These three preferred outcomes sometimes contributed to one another (quote 2). If preferred outcomes were already fulfilled, the organizational elements and elements of trust were experienced as less important.

• Quote 1: “I had heard about homesickness before, homesickness, what nonsense is that? Nonsense. But then I actually was homesick. Oh, if only I could go home, if only I could go home. That’s my only wish.” (female patient)

• Quote 2: “She was rather weakened, but seeing how much my mother likes to be home again, in her own environment where she feels safe, with her cat, and the visits of alternately us and the formal care givers that comforts me.” (a patient’s son)

Organization of Transitional Care

Study participants indicated that various organizational aspects contributed to optimal transitional care; involvement of the informal caregiver, attention for the patient’s and informal caregiver’s wishes and situation, information provision towards the patient and/ or informal caregiver and professionals being informed. These organizational aspects enabled participants to reach the preferred outcomes.

The first mentioned element in organization was involvement of the informal caregivers in transitional care. Informal caregivers were important in receiving information, since some of the patients could not remember or understand all information given. This made patients feel safe (quote 3). Furthermore, involvement of the informal caregiver helped the patient to go home as soon as possible; often part of the care needed after discharge could be given by the informal caregiver. One patient suggested to structurally have discharge conversations between hospital care providers, patient and informal caregivers.

• Quote 3: “I was lying there and it all just happened to me. That’s how it felt. Again, I had back-up from my daughters of course. I actually wasn’t a patient on my own, I still had those three girls around me” “I am a nervous patient. I am quickly worried about something as soon as something is going on, so I have one of the three.” (female patient).

Secondly, attention for the patients’ and informal caregivers’ wishes and situation was an important element of organization facilitating the preferred outcomes. However, the amount of attention being sufficient differed per person; some patients highly valued privacy. One informal caregiver explained she especially found home care nurses’ attention for her father’s situation important; he was fully dependent on these nurses (quote 4). Variety in professionals caring for a patient was experienced as a barrier towards attention for personal wishes and situation.

• Quote 4: “You are completely dependent on whoever visits you so you need people who understand the situation someone is in. Some just do their job and others really understand my father’s situation.” (a patient’s daughter).

Thirdly, several participants stressed the importance of them being informed. They wanted to receive information about the patient’s health status, applicable health indicators, treatment risks, expected date of discharge, reasons for discharge, aftercare and medication prescriptions. This information helped patients to take control over their own rehabilitation and reach an adequate health status (quote 5) and to feel safe. However, too many spoken information at once was counterproductive and inconclusive information was displeasing.

• Quote 5: “I want to know what’s going on with me. I want to stay in control. And make sure that I get well as quickly as possible.” (female patient).

Fourthly, several participants indicated the importance of professionals being informed. Some patients illustrated that the General Practitioner (GP) and home care nurses being informed about their discharge and situation was crucial to recover and a prerequisite to go home. Several participants thought this supply of information was the responsibility of the hospital care providers (quote 6).

• Quote 6: “I think the GP should know what’s going on, so if I call him, he knows why he should come. At hospital discharge, a message is supposed to go to the GP immediately I shouldn’t have to call him.” (female patient).

Trust in professional care providers

Besides organization of transitional care, aspects of trust contributed to the preferred outcomes, most explicitly to feeling safe. Firstly, empathy of professional care providers was an important element of trust. It was a recurring topic in several interviews and seemed to greatly influence participants’ overall experience of the transition of care (quote 7) and feelings of safety. Medical or organizational flaws often were forgiven if treated with empathy (quote 8).

• Quote 7: “When you lie in such a hospital you are very… sad, sad you could call it. The kindness of the people, that affects you most. I mean, you don’t need a pill.” (patient 10: 89 years old woman)

• Quote 8: SK: “And if we have a look at the people who come here to help, [do you have] trust in them as well?” Informal caregiver: “Yes, [they are] sweet, very sweet. They always wait until that device [probe feeding pump] works well. Well, today it went completely wrong. But that wasn’t her fault.” (a patient’s wife).

Secondly, concrete assurance that continuity of care was organized was important. Study participants felt unsafe when this assurance was missing, for example when primary care providers were inaccessible during holidays or when there was no guarantee the GP would read the discharge letter from the hospital in time. While some participants approached professionals to obtain this assurance themselves, others were resistant to take initiative. Assurance could be given by hospital care providers orally (quote 9), but also by primary care providers physically delivering suitable care immediately after discharge.

• Quote 9: “I said ‘doctor, you wouldn’t let me go home this ill right? He said ‘no, we surely won’t, whenever you go home, you will be able to move on’, and indeed they took care of that.” (female patient)

The third element important in trust was meeting expectations around hospital discharge. If expectations were not met, this negatively affected patients’ and informal caregivers’ trust in the professional care provider (quote 10). Several patients and informal caregivers had only low expectations (quote 11), for example if they believed their hospital stay was too short to expect much. These expectations were met or exceeded and their trust remained.

• Quote 10: “If you’re a GP you should have a little trust towards your patients, gaining trust and he does not. I never met this man, maybe he is very kind and maybe he is very busy, I do take that into account, but the first thing a GP should do is ask how it has been , he didn’t do so.” (a patient’s son).

• b “A hospital is like a large family, exactly like it. Do you like the food? Yes, one thing you like better than another. At home you don’t always get good food either. And there’s a lot of things like that. They help you; they try to please you as much as possible. But yes, sometimes something happens that you don’t like that much.” (female patient).

These findings from the perspective of vulnerable older patients and informal caregivers are summarized in the conceptual model in Figure 1.

Figure 1: Conceptual model of transitional care for vulnerable older patients.

Perspective of Hospital and Home Care Nurses

No additional elements important in transitional care for vulnerable older patients were found from the perspective of hospital and home care nurses. Nurses mentioned the same organizational elements. Involvement of informal caregivers contributes to improvement of care (quote 12). Attention for personal wishes/ situation was found important (quote 13) and informing patients and informal caregivers was also seen as important (quote 14), especially to make informal caregivers feel safe. Informing professionals was frequently discussed, because it contributes to improvement of care as well as to assurance of both the professionals and patients (quote 15). Absence of a strict organization of the transition of care was called dangerous. Nurses believed that clearly formulated interventions could be implemented to achieve well organized transitional care.

The nurses discussed the preferred outcomes and importance of trust less explicitly. However, the role of empathy (quote 12) and assurance (quote 15) in trust and all three the preferred outcomes (quote 12, 13, 15) seemed underlying notions in their discussions.

• Quote 12: “It’s just when you have time for those people and you sit down next to them [informal caregivers], with a book and writing things down, I really have the feeling that you are taking away a lot [of worries] already, and that the care expires in a better way” (hospital nurse geriatrics) “Yes, we experience that at home as well.” (home care nurse).

• Quote 13: “I had a client who was, well I don’t know if she was already seventy, but she was very vulnerable, and was allowed to go home, because she was rehabilitated and well. However, she got a big wound on her foot, and she had a polluted house. So, I said she can’t go home” (home care nurse).

• Quote 14: “We put the provisional date of discharge, the target date, on the board in the room, so the family knows about it like that.” (hospital nurse geriatrics).

• Quote 15: “if I call you and say ‘so, what have you been able to do, this and that’, then I’m like ‘oh nice’, you know, it is going well, so she can go home and I know it will go well at home too. That lady knows that the home care nurse knows, sometimes I can already tell who will come, at what time they will come, and that’s just, yes, very nice.” (Home care nurse).

Discussion

Vulnerable older patients’ and informal caregivers’ preferred outcomes in transitional care are the patient going home, the patients reaching adequate health and both of them feeling safe. They indicated organizational elements and elements of trust are needed to reach these preferred outcomes. The organization of transitional care for vulnerable older patients was not always optimal. However, the effect of organizational difficulties on the preferred outcomes remained limited if the elements of trust were fulfilled.

Literature as well describes organization of care for vulnerable older patients, often with complex health problems, to be increasingly challenging . Our results suggest that with this challenge trust will become more important in fulfilling the preferred outcomes. This fits the current trend towards person-centered care, as described by The American Geriatric Society Expert panel [24]. Professional care providers, as well as researchers and policy writers should take into account the importance of patients’ and informal caregivers’ trust and give this a place in their work.

Hospital and home care nurses recognized the same organizational elements. They also discussed trust and the preferred outcomes, although less explicitly. This indicates patients’ and informal caregivers’ perspectives are a valuable contribution to research.

To our knowledge we are the first to model the organization of care and trust as two aspects that count up to fulfilment of preferred outcomes in transitional care for vulnerable older patients. However, two previous studies may imply parts of our model. Firstly, a recent Dutch study, based on interviews with chronically ill patients after hospital discharge and readmission, described organizational aspects similar to the ones we found as well the importance of continuity in professionals and the feeling of being ready to go home. These last two respectively imply trust and the preferred outcome feeling safe from our results . Secondly, a meta-analysis by Allen et al. explained that besides optimizing efficiency in transitional care for older patients, personal attention and social processes are important .

The single elements of organization, involvement of the informal caregiver, attention for personal wishes/situation, informing patients and/or informal caregivers and informing professionals, were more often described in literature about older patients’, informal caregivers’ and professionals’ perspectives on transitional care for vulnerable older patients [15,26,27]. Mainly studies that focused on patients’ perspectives described the importance of trust in professionals during transitional care [13,28]. The preferred outcomes going home and adequate health were indicated before by patients in geriatric rehabilitation [29].

A limitation of the study could be selection bias. There is no data available upon the reason for 6 vulnerable older patients to reject upon participation, but they might have been more ill or less satisfied then participating patients. Nevertheless, baseline characteristics show variety in study participants.

The focus is on patients’ and informal caregivers’ perspectives are one of our study’s strengths. Exploring their perspectives facilitated us to identify what was different from the more often studied perspectives of professional care provides. Besides, combining perspectives of patients and informal caregivers reflected how patients’ perspectives are not independent of their informal caregivers’ perspectives in reality . A second strength was the minimization of recall bias by performing the interviews within two weeks after discharge. Besides, we noticed that the informal caregivers helped patients to remember whatever they had forgotten.

Thirdly, participants were unaware of our secondary aim to compare perspectives of vulnerable older patients and informal caregivers to perspectives of nurses. In this way, participants stayed true to their own perspective.

Conclusion

In conclusion, the present study contributed to a deeper understanding of what is needed to optimize transitional care for vulnerable older patients with home care indication. Consistency among our study participants and literature upon relevant organizational elements in transitional care might indicate these should be structurally implemented into practice. However, based on our results, even well-organized transitional care especially fulfilled vulnerable older patients’ and their informal caregivers’ preferred outcomes if they have trust in the involved professionals.

Regarding the challenge of organizing increasingly complex transitional care for vulnerable older patients, the focus on optimizing trust becomes even more important. Practicing healthcare providers, as well as future research, policies and innovations should allow for this trust between people to have a place in healthcare organization.

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Doctors Aware of Patient Difficulties Affording Medical Care

 

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Doctors know about patients’ trouble with bearing therapeutic consideration and consider out-of-take costs in their basic leadership, as indicated by an article distributed in an enhancement to the May 7 issue of the Annals of Internal Medicine.

Susan L. Perez, Ph.D., M.P.H., from California State University in Sacramento, and associates talked with 20 interior prescription doctors and reviewed 621 inside drug doctor individuals from the American College of Physicians to inspect the elements that impact dialog and thought of expense amid patient experiences.

The analysts distinguished four topics from the meetings: Physicians know that patients are battling with the expenses of restorative consideration; depend on pieces of information from patients that allude to cost affectability; depend on understanding to foresee conceivably surprising expense medicines; and know about the money related exchange off that patients make to pay for consideration.

Canagliflozin Seems Effective for Patients With T2DM, Kidney Disease

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Canagliflozin is related with a decreased hazard for renal and cardiovascular occasions for patients with sort 2 diabetes and kidney infection, as indicated by an investigation distributed online April 14 in the New England Journal of Medicine to concur with the International Society of Nephrology World Congress of Nephrology, held from April 12 to 15 in Melbourne, Australia.

In a twofold visually impaired, randomized preliminary, Vlado Perkovic, M.B., B.S., Ph.D., from the George Institute for Global Health at the University of New South Wales Sydney, and associates arbitrarily relegated patients with sort 2 diabetes and albuminuric unending kidney illness to get either canagliflozin (100 mg day by day) or fake treatment.

After an arranged break investigation, the preliminary was halted at an opportune time the proposal of the information and security checking board of trustees. The scientists found that by then, 4,401 patients had experienced arbitrary task with a middle follow-up of 2.62 years.

One Short, Brisk Walk a Day May Keep Arthritis at Bay

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Under 10 minutes per day of lively strolling can help avert handicap in individuals with joint inflammation torment in their knee, hip, lower leg or foot, specialists report. Only one hour seven days of lively physical movement “is under 10 minutes per day for individuals to keep up their autonomy. She’s a teacher of preventive medication at Northwestern University’s Feinberg School of Medicine in Chicago. “This base limit may persuade latent more established grown-ups to start their way toward a physically dynamic way of life with the wide scope of medical advantages advanced by physical action,” Dunlop included a college news discharge. She and her group broke down four years of information from in excess of 1,500 more seasoned grown-ups in Baltimore, Pittsburgh, Columbus, Ohio, and Pawtucket, R.I., who had agony, hurting or solidness in their lower joints from osteoarthritis however were at first free of inability.

The members’ dimensions of physical movement were checked utilizing a wearable gadget. An hour seven days of moderate-to-enthusiastic physical movement decreased their danger of inability, the investigation found. In particular, the movement decreased the danger of strolling also gradually to securely cross a road by 85 percent, and their danger of not having the capacity to do day by day living exercises – for instance, morning schedule errands, for example, strolling over a room, washing and dressing – by about 45 percent. Before the finish of the four years, 24 percent of members who did not get a week by week hour of energetic physical action were strolling too gradually to securely cross the road, and 23 percent experienced issues playing out their morning schedules, as indicated by the examination.

A Better Cardiac Pump for People With Heart Failure?

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Another rendition of an implantable heart siphon could cut the danger of blood clumps, draining and stroke in patients with cutting edge heart disappointment as per an investigation subsidized by the gadget’s creator. The investigation included in excess of a thousand patients who got either Abbott Inc’s. HeartMate 3 remaining ventricular help gadget (LVAD) or the HeartMate II. Following two years, around 75 percent of those in the HeartMate 3 assemble were as yet alive, had not endured an impairing stroke and did not require another activity to evacuate a breaking down gadget, contrasted and almost 61 percent in the HeartMate II gathering, the investigation found. “These last outcomes, based on what is by a wide margin the biggest LVAD preliminary at any point directed, show the clinical prevalence of the HeartMate 3 contrasted and its ancestor, the HeartMate II,” said lead think about creator Dr. Mandeep Mehra. He’s medicinal chief at the Heart and Vascular Center at Brigham and Women’s Hospital in Boston.

The investigation was introduced Sunday at the American College of Cardiology’s Annual Scientific Session, in New Orleans, and distributed online in the New England Journal of Medicine. In heart disappointment, harmed hearts turn out to be excessively feeble to productively siphon blood. The better than ever HeartMate ought to broaden the lives of numerous heart disappointment patients, said one pro detached to the examination.

Transgender Hormone Therapy Could Pose Heart Dangers

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People who get hormone treatment amid sexual orientation change treatment may confront an a lot higher hazard for creating coronary illness new Dutch research alerts. In light of our outcomes, we ask the two doctors and transgender people to know about this expanded cardiovascular hazard said examination creator Dr. Nienke Nota, a specialist in the branch of endocrinology at the Amsterdam University Medical Center. It might be useful to decrease hazard factors by ceasing smoking, working out, eating a sound eating regimen and getting more fit, if necessary, before beginning treatment, and clinicians should keep on assessing patients on a continuous premise from that point Nota said in an American Heart Association news discharge.

The finding originated from an audit of therapeutic records concerning in excess of 2,500 transgender ladies and almost 1,400 transgender men experiencing sexual orientation progress in Holland. All had begun to get hormone treatment eventually somewhere in the range of 1972 and 2015. Examiners followed heart entanglements for a normal of nine years among trans ladies patients, who had been allocated a male sexual orientation during childbirth and after that took hormone treatment to end up female. Stroke hazard and heart assault chance among such trans ladies was pegged as more than twofold than it was among other ladies, while stroke chance alone was twice that of men.

 

 

 

 

 

The Lowdown on E-Cigarette Risks for Kids

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The Lowdown on E-Cigarette Risks for Kids

The worry over vaping has kept on working as e-cigarettes have turned out to be progressively mainstream, particularly with children and youngsters. Vaping – breathing in fluid nicotine vapors – was first promoted as an approach to enable grown-ups to stop smoking. In any case, more youthful individuals, including tweens, immediately seized on it as a route around customary cigarettes, some pulled in by the treat flavors and brilliant bundling. A few specialists have detailed that vaping is simply one more street to nicotine habit.

Research has effectively discovered that e-cigarette use among school-matured youngsters is developing altogether, and that kids presented to e-cigarette promotions are bound to attempt them. Furthermore, these advertisements are all over the place, from the web and retail locations to TV and motion pictures. The risk to youngsters’ wellbeing begins early. Somewhere in the range of 2012 and 2015, the National Poison Data System dealt with in excess of 29,000 calls about youngsters under age 6 being presented to nicotine items. Children presented to e-cigarettes had multiple times the chances of being hospitalized and more than twofold the chances of having a serious result than those presented to cigarettes.

In spite of the fact that these numbers have descended gratitude to laws requiring youngster safe bundling and developing attention to the dangers related with e-cigarettes, specialists state that fluid nicotine keeps on representing a genuine hazard for youthful kids specifically. The U.S. Sustenance and Drug Administration has as of late increase its reaction to kid-accommodating advertising strategies of producers and illicit offers of e-cigarettes to kids. Guardians should likewise do their part by conversing with children about the perils of all cigarettes since the beginning. Examine the advertisements they’re probably going to see and demystify their allure.