Unraveling sleep respiratory dysfunction in amyotrophic lateral sclerosis: Beyond the apnea-hypopnea index and sleep-related hypoxia.

The timely introduction of non-invasive ventilation (NIV) is extremely relevant in the multidisciplinary management of patients affected by amyotrophic lateral sclerosis (ALS) and is based on the proper identification of red flags for early diaphragmatic exhaustion. Polygraphic sleep recording may provide insightful information on the ongoing respiratory impairment; in particular, atypical breathing patterns need to be recognized, as the application of current guidelines for sleep-related hypoxemia or sleep apnea may be insufficient for detecting early signs of diaphragmatic fatigue. We report the case of a 51-year-old man affected by ALS who was asymptomatic for breathing impairment, but whose nocturnal polysomnographic recording, despite not significant for obstructive sleep apnea nor for conventional hypoventilatory patterns, strongly suggested initial respiratory failure, as lately confirmed by the pulmonary follow-up. We discuss the advantages of including sleep recording in the clinical work-up of patients affected by ALS.

Effectiveness and cost-effectiveness of a collaborative deprescribing intervention of proton-pump-inhibitors on community-dwelling older adults: Protocol for the C-SENIoR, a pragmatic non-randomized controlled trial.

INTRODUCTION: Worldwide, demographic ageing is a major social, economic and health challenge. Despite the increase in life expectancy, elderly often live with multiple chronic conditions, exposing them to multiple medications. Concerns have been raised about the growing issue of inappropriate long-term usage of proton-pump inhibitors (PPI), which have been associated with adverse outcomes and increased healthcare costs. Deprescribing is a recommended intervention to reduce or withdraw medicines that might be causing harm or might no longer be of benefit. This protocol details a trial to assess the effectiveness and cost-effectiveness of a collaborative deprescribing intervention of PPI among community-dwelling elderly, involving community pharmacists and general practitioners. METHODS AND ANALYSIS: A pragmatic, multicentre, two-arm, non-randomised controlled trial of a structured PPI collaborative deprescribing intervention in the primary care setting with a 6-month follow-up will be conducted. Patients must be 65 years old or older, live in the community and have been using PPI for more than 8 weeks. We hypothesize that the intervention will reduce the PPI usage in the intervention group compared to the control group. The primary outcome is the successful discontinuation or dose decrease of any PPI, defined as a statistically significant absolute 20% reduction in medication use between the intervention and control groups at 3- and 6-month follow-ups. An economic evaluation will be conducted alongside the trial. This study was approved by the Ethics Research Committee of Nova Medical School, NOVA University of Lisbon and by the Ethics Committee from the Local Health Unit Alto Minho, Portugal. DISCUSSION: This pragmatic trial will provide evidence on the effectiveness and cost-effectiveness of a patient-centred collaborative deprescribing intervention in the community setting in Portugal. It will also inform improvements for the development of future multi-faceted interventions that aim to optimise medication for the community-dwelling elderly. CLINICAL TRIAL REGISTRATION: ISRCTN 49637686.

Real-World Effectiveness in Hypertension and Hyperlipidemia Collaborative Management between Pharmacies and Primary Care in Portugal: A Multicenter Pragmatic Controlled Trial (USFarmácia®).

There is evidence of the efficacy of collaborative health interventions with pharmacies and primary care providers but little of its real-world effectiveness. We aimed to assess the effectiveness and discuss the design and challenges of hypertension and hyperlipidemia management between pharmacies and primary care providers using real-world data exchange between providers and experimental bundled payment. This was a pragmatic, quasi-experimental controlled trial. We collected patient-level data from primary care prescription claims and Electronic Medical Record databases, a pharmacy claims database, and patient telephone surveys at several time points. The primary outcomes were changes in blood pressure and total cholesterol. We used matched controls with difference-in-differences estimators in a Generalized Linear Model (GLM) and controlled interrupted time series (CITS). We collected additional data for economic and qualitative studies. A total of 6 Primary Care Units, 20 pharmacies, and 203 patients entered the study. We were not able to observe significant differences in the effect of intervention vs. control. We experienced challenges that required creative strategies. This real-world trial was not able to show effectiveness, likely due to limitations in the primary care technology which affected the sample size. It offers, however, valuable lessons on methods, strategies, and data sources, paving the way for more real-world effectiveness trials to advance value-based healthcare.

Non-alcoholic Wernicke's Encephalopathy mimicking neuromyelitis optica spectrum disorder in a young woman: a case report and literature review.

Wernicke's encephalopathy is an under-recognized life-threatening disease caused by thiamine (vitamin B1) deficiency. It has historically been related to chronic alcoholic intake but other causes of malnutrition, such as invasive gastric surgery and hyperemesis, have been linked to the onset of this illness over the years, often presenting with atypical clinical manifestations.  Herein we report a case of a young obese woman affected by non-alcoholic Wernicke's Encephalopathy following a minimally invasive gastrointestinal surgery. She showed an unusual clinical profile characterized by prominent subacute neuro-ophthalmological involvement which combined to her juvenile age, overweight condition and brain lesions, have made diagnosis challenging due to similarities with Neuromyelitis Optica Spectrum Disorder.   Our case underscores the relevance of prompt diagnosis in order to prevent the development of irreversible neuropathological changes and to avoid the use of a long-term immunosuppressive treatment.

Effectiveness of a collaborative diabetes screening campaign between community pharmacies and general practitioners.

AIM: To evaluate the impact of a collaborative screening campaign on the prevalence of pre-diabetes and diabetes among the screened population. METHODS: A Longitudinal, multicentre study was developed. The Finnish Diabetes Risk Score (FINDRISC) was applied to the eligible population in the participating community pharmacies. Individuals with a FINDRISC score ≥ 15, were eligible to measure their glycated haemoglobin (HbA1c) level at the community pharmacy. If HbA1c≥ 5.7%, participants were referred to a general practitioner (GP) appointment for potential diagnosis of Diabetes. RESULTS: Out of 909 screened subjects, 405 (44.6%) presented a FINDRISC score ≥ 15. Among the latter, 94 (23.4%) had HbA1c levels that made them eligible for GP referral, of which 35 (37.2%) completed the scheduled appointments. 24 participants were diagnosed with pre-diabetes, and 11 with diabetes. The prevalence was estimated at 2.5% (CI95% 1.6-3.8%) and 7.8% (CI95% 6.2-9.8%) for diabetes and pre-diabetes, respectively. CONCLUSION: This collaborative model has proved to be effective in the early detection of diabetes and pre-diabetes. Joint initiatives between health professionals can play a pivotal role in the prevention and diagnosis of diabetes, which may lead to a reduction on the burden to health system and society.

Real-World Impact of Transferring the Dispensing of Hospital-Only Medicines to Community Pharmacies During the COVID-19 Pandemic.

OBJECTIVES: In Portugal, the dispensing of most outpatient specialty medicines is performed exclusively through hospital pharmacies and totally financed by the National Health Service. During the COVID-19 first wave, the government allowed the transfer of the dispensing of hospital-only medicines (HOMs) to community pharmacies (CPs). This study aimed to measure the value generated by the intervention of CP in the dispensing of HOM. METHODS: A single-arm, before-and-after study with 3-month follow-up was conducted enrolling a randomly selected sample of patients or caregivers with at least 1 dispensation of HOM through CP. Data were collected by telephone interview. Main outcomes were patients' self-reported adherence (Measure Treatment Adherence), health-related quality of life (EQ-5D 3-Level), satisfaction with the service, and costs related to HOM access. RESULTS: Overall 603 subjects were recruited to participate in the study (males 50.6%) with mean 55 years old (SD = 16). The already high mean adherence score to therapy improved significantly (P < .0001), and no statistically significant change (P > .5757) was found in the mean EQ-5D score between baseline (0.7 ± 0.3) and 3-month follow-up (0.8 ± 0.3). Annual savings account for €262.1/person, arising from travel expenses and absenteeism reduction. Participants reported a significant increase in satisfaction levels in all evaluated domains-pharmacist's availability, opening hours, waiting time, privacy conditions, and overall experience. CONCLUSIONS: Changing the dispense setting to CP may promote better access and satisfaction. Moreover, it ensures the persistence of treatments, promotes savings for citizens, and reduces the burden of healthcare services, representing a crucial public health measure.

Drug shortages in community pharmacies: Impact on patients and on the health system.

BACKGROUND: Worldwide, drug shortages are a critical public health concern. Consequences range from inconvenience and distress to more serious concerns related to negative clinical, humanistic and economic outcomes. OBJECTIVE: This study aimed to investigate the impact of drug shortages at the community pharmacies on patients and on the health system in Portugal. METHODS: A national, cross-sectional, multicenter study was conducted in Portuguese community pharmacies during April 2019. The proportion of patients reporting drug shortages, types of drugs affected and consequent economic burden to patients and the health system were estimated. Regional and urban setting stratification was performed. RESULTS: A total of 71.1% of pharmacies participated in the study and 22,830 patient surveys were retrieved. About 52.2% of patients experienced a drug shortage in the past 12 months; 21.5% had to see a physician to change the prescription and 5.7% declared treatment discontinuation because of this shortage. The estimated economic impact of shortages related to additional physician appointments varied between €2.1-€4.4 million for patients and €35.3-€43.8 million for the National Health Service. Drug shortages were mostly felt in rural and inner regions and least felt in the islands. CONCLUSION: This national study showed that community pharmacy drug shortages are a national problem with negative consequences on patients and the health system, which need to be tackled and mitigated.

Deprescribing Interventions among Community-Dwelling Older Adults: A Systematic Review of Economic Evaluations.

BACKGROUND: Deprescribing can reduce the use of inappropriate or unnecessary medication; however, the economic value of such interventions is uncertain. OBJECTIVE: This study seeks to identify and synthetise the economic evidence of deprescribing interventions among community-dwelling older adults. METHODS: Full economic evaluation studies of deprescribing interventions, conducted in the community or primary care settings, in community-dwelling adults aged ≥ 65 years were systematically reviewed. MEDLINE, EconLit, Scopus, Web of Science, CEA-TUFTS, CRD York and Google Scholar databases were searched from inception to February 2021. Two researchers independently screened all retrieved articles according to inclusion and exclusion criteria. The main outcome was the economic impact of the intervention from any perspective, converted into 2019 US Dollars. The World Health Organization threshold of 1 gross domestic product per capita was used to define cost effectiveness. Studies were appraised for methodological quality using the extended Consensus on Health Economics Criteria checklist. RESULTS: Of 6154 articles identified by the search strategy, 14 papers assessing 13 different interventions were included. Most deprescribing interventions included some type of medication review with or without a supportive educational component (n = 11, 85%), and in general were delivered within a pharmacist-physician care collaboration. Settings included community pharmacies, primary care/outpatient clinics and patients' homes. All economic evaluations were conducted within a time horizon varying from 2 to 12 months with outcomes in most of the studies derived from a single clinical trial. Main health outcomes were reported in terms of quality-adjusted life-years, prevented number of falls and the medication appropriateness index. Cost effectiveness ranged from dominant to an incremental cost-effectiveness ratio of $112,932 per quality-adjusted life-year, a value above the country's World Health Organization threshold. Overall, 85% of the interventions were cost saving, dominated usual care or were cost effective considering 1 gross domestic product per capita. Nine studies scored > 80% (good) and two scored ≤ 50% (low) on critical quality appraisal. CONCLUSIONS: There is a growing interest in economic evaluations of deprescribing interventions focused on community-dwelling older adults. Although results varied across setting, time horizon and intervention, most were cost effective according to the World Health Organization threshold. Deprescribing interventions are promising from an economic viewpoint, but more studies are needed.

Physical activity promotion in community pharmacies: pharmacists' attitudes and behaviours.

BACKGROUND: Health systems and their professionals play a key role in the promotion and maintenance of behaviours contributing to increased physical activity levels. Pharmacists are well placed within communities, making them an accessible source to provide brief advice to people on how to be more physically active. OBJECTIVE: This study aimed to characterize physical activity promotion actions taking place in the Portuguese community pharmacies, as well as the major facilitators and barriers faced by pharmacists in their daily practice. METHODS: A cross-sectional study based on an online questionnaire targeting community pharmacists was developed based on COM-B model and the Theoretical Domains Framework (TDF) and distributed by email to 94% of the Portuguese pharmacies. RESULTS: In total, 396 complete responses from community pharmacists were obtained. Three out of four participants reported to promote physical activity in their daily routine, of which 87.7% reported doing it in only a few attendances. The majority (92.3%) mentioned to provide information orally, with walking being the activity most promoted (99.4%). More active and younger pharmacists were more likely to promote physical activity. Nearly all pharmacists (98.7%) believed it was important or very important to practice regular physical activity for the health, but only 41.4% of the respondents were able to correctly identify the WHO general recommendations for physical activity. The lack of coordination with other healthcare professionals (M=3.35; SD=1.11), lack of interest by customers (M=3.25; SD=1.09) and lack of time (M=3.06; SD=1.10) were the main barriers to physical activity promotion, all scoring above the scale mid-point (i.e., 3). CONCLUSIONS: Physical activity promotion in the Portuguese community pharmacies is still not present as daily activity. Younger pharmacists seem to be a generation that better understand this need and could easily integrate this practice in their daily routine. Possibilities for including pharmacies and pharmacists as promoters of physical activity in the primary health care sector in the future are discussed in the light of these findings.

Effectiveness of a pharmacist-led intervention on inhalation technique for asthma and COPD patients: The INSPIRA pilot cluster-randomized controlled trial.

INTRODUCTION: Asthma and COPD are leading causes of disability-adjusted life-years worldwide representing a huge burden on the health system and among patients. One of the reasons for the lack of disease control is poor inhalation technique, with impact on quality of life and symptom control. OBJECTIVE: To assess the effectiveness of a community pharmacist-led educational intervention on asthma and COPD patients' inhalation technique. METHODS: The INspira study is a 6-month pilot cluster randomized controlled trial, conducted in community pharmacies of Portugal, enrolling adults aged 18 years or older, with a self-reported diagnosis of asthma or COPD and on inhaled therapy. Pharmacies were randomly allocated to Intervention or Control group. Intervention focused mainly on inhalation technique education via demonstration and repetition. Primary outcome was the proportion of patients scoring 100% in at least one inhaler. RESULTS: From January to November 2019, 48 pharmacies recruited 201 asthma and COPD patients, of which 132 completed the 6-month follow-up. At the end of follow-up, the odds of intervention group patients score 100% compared to the control group were 5.63 (95% CI, [2.21; 14.35]) in all inhalers in use and 6.77 (95% CI, [2.52; 18.20]) considering at least one inhaler. Intervention group patients reported having a significantly lower number of scheduled appointments compared with the control group (OR = 0.17; 95% CI, [0.037; 0.79]; p = 0.0135). No other significant differences were found between groups. CONCLUSION: This pilot study suggested that pharmacist interventions can improve patients' inhalation technique, with possible positive impact in healthcare resource use.

Time-trend analysis of medicine sales and shortages during COVID-19 outbreak: Data from community pharmacies.

BACKGROUND: COVID-19 is a worldwide public health concern. Disruptions in the drug market are expected and shortages might worsen. Community pharmacies can contribute to early identification and report of medicines' supply and demand issues. OBJECTIVE: The aim of this study is to characterize the impact of the COVID-19 outbreak on outpatient medicines' sales and shortages. METHODS: A retrospective, time-trend analysis of medicine sales, shortages and laboratory-confirmed COVID-19 cases was performed from February 1st to April 30th, 2020, and its homologous period (regarding sales only). A detailed analysis of 6 pharmaceutical substances was performed. All data were subjected to rescaling using the min-max normalization method, in order to become comparable. Data analysis was performed using Microsoft® Excel. RESULTS: The pandemic resulted in an increase in medicines' demand and reported shortages during the early stage of the outbreak. The maximum proportion of medicine sales was registered on March 13th, 2020, 4 days after the WHO declared COVID-19 a pandemic. By the end of March, sales have already dropped to proportions similar to those of 2019. The maximum proportion of drug shortages was reached about one week after the sales peak and by the end of the study period were below those recorded in the pre-COVID-19 period. The analyzed drugs were paracetamol, ascorbic acid, dapagliflozin plus metformin, rosuvastatin plus ezetimibe, formoterol, and hydroxychloroquine, as these pharmaceutical substances registered the highest growth rate in sales and shortages when compared to the same period in the previous year. Hydroxychloroquine showed the most different pattern trends on sales and shortages of these medicines. CONCLUSIONS: Pharmacies can provide timely and real-world data regarding sales and shortages. The adopted measures to guarantee the continuous supply of the medicine market seem to have worked. The long-term impacts of this pandemic are unknown and should continue to be closely monitored.

Who are the ostomy patients and caregivers attending Portuguese community pharmacies? A cross-sectional study.

BACKGROUND: In 2017, ostomy patients gained access to ostomy products in community pharmacies that are fully reimbursed by the Portuguese National Health Service. This impacted the daily lives of people with ostomy and opened a new market of products and services for pharmacies. However, little is known about the sociodemographic and clinical profile of ostomy patients. This study aims to characterize people with ostomy and their caregivers, evaluate access and satisfaction with the pharmacy and explore participants' expectations regarding services and counselling. METHODS: This was an observational, cross-sectional, multicentre study involving pharmacy users who acquired ostomy products in Portuguese community pharmacies. Data were collected through a confidential self-report questionnaire between June and August 2019. RESULTS: Approximately 56% of the participants were ostomy patients, of whom 65.9% were men. The average age of participating ostomy patients was 65.5 years old (SD = 12.9), and near 80% were retired/pensioners. Caregivers were mostly women (81.7%). More than half of the caregivers were employed and acquired products for a direct family member. Three in every four surgical interventions were consequences of cancer. Intestinal ostomy was the most common intervention (78.3%). More than 93% were satisfied with the acquisition of ostomy products at the pharmacy. Approximately 48.2% of ostomy patients received care from a specialized nurse. CONCLUSION: This study describes the profile of people with ostomy and their caregivers who attend community pharmacies in Portugal. Participants' perceptions of the utility of different proposed services and pharmacist knowledge, as well as the low coverage of ostomy nursing care, highlight the opportunity for an extended role of pharmacists among this group.

A new model for pharmacies? Insights from a quantitative study regarding the public's perceptions.

BACKGROUND: Worldwide community pharmacies are shifting their role in the healthcare system from simple medication dispensers to health care providers. High levels of satisfaction with pharmacy services were found in previous studies. This study has two main goals. The primary goal is to describe the levels of satisfaction and knowledge regarding pharmacy services in Portugal. The secondary goal is to explore the perceptions and the utilisation of pharmacy services by the Portuguese. This statement includes exploring the impact of a set of variables on both perceptions and uses of pharmacies in regard to services that are currently offered as well as to new services that may be provided in the future. METHODS: A face-to-face survey of closed-ended questions was applied to a nationwide representative sample of the Portuguese population in September 2015. The sample was weighted based on population distribution across regions, habitat, age and gender. Data analysis comprises descriptive statistics and Multiple Correspondence Analysis to explore different typologies of respondent's orientation toward community pharmacy. RESULTS: A total of 1114 interviews comprised the study. Of the respondents, 36% used the pharmacy as a first resource when seeking to treat a minor ailment, and 54% reported that they use the pharmacy as a first resource when seeking answers about medicines. Of those who visited their pharmacy at least once in the previous year, 94% were either globally satisfied or very satisfied. The level of acknowledgement of pharmacy services' was also high among the Portuguese. Of the participants, 29% considered there could be more services available in pharmacies that are currently provided by other health care facilities. The construction of a typology of orientations towards community pharmacy practice resulted in three outcome groups: "Motivated" (63%), those with a connection to a pharmacy; "Settled" (23%), mainly those who had a pharmacy nearby; and "Demobilised" (14%), those who are weakly tied to a pharmacy. CONCLUSIONS: The vast majority of the Portuguese population has a strong positive attitude towards their community pharmacy, as expressed by the high levels of satisfaction with, and positive evaluation of, the pharmacy's services.

Prevalence and predictor factors of respiratory impairment in a large cohort of patients with Myotonic Dystrophy type 1 (DM1): A retrospective, cross sectional study.

INTRODUCTION: Respiratory complications are relevant in DM1, leading to a significantly increased morbidity and mortality risk in these patients; however, so far only few studies concerning respiratory function have been conducted in DM1 patients. We report a retrospective, multicenter, cross sectional study on a large cohort of DM1 patients widely characterized in the phenotype, to assess prevalence and identify predictors of restrictive respiratory syndrome. METHODS: 268 DM1 subjects aged >18 years, who had recently performed spirometric tests were included; restrictive syndrome was diagnosed if forced vital capacity (FVC) <80% of predicted. This cut-off was used for statistical univariate and multivariate analysis. RESULTS: 51.9% patients showed a restrictive syndrome, and half of them had indication to non-invasive ventilation (NIV), yet only 50% resulted compliant to NIV. CTG expansion size in leukocytes, clinical muscle severity, most functional parameters of respiratory muscle involvement, presence of cardiac conduction disturbances, pacemaker (PMK), exertion dyspnea, obstructive sleep apnea, and indication and compliance to NIV were all significantly associated with restrictive syndrome at the univariate analysis; in the multivariate model only the first two factors resulted independent predictors. DISCUSSION: A high prevalence of restrictive syndrome in our DM1 cohort, mainly due to respiratory muscles weakness, was observed and documented; the severity of muscle impairment and the CTG expansion size confirmed to be independent predictors of respiratory restriction. Our data suggest that optimization of respiratory therapeutic management, particularly regarding launching of NIV, might help to reduce the rate of deaths due to respiratory complications in DM1.

Real-world prevalence of mild to moderate hypoglycemic episodes in type 2 diabetes in Portugal: Results from the HIPOS-PHARMA study.

AIMS: This study aimed to characterize and estimate prevalence and frequency of mild to moderate hypoglycemia and potentially associated factors in a population of type 2 diabetes mellitus (T2DM) patients treated at ambulatory care level. METHODS: HIPOS-PHARMA was a nationwide observational, cross-sectional, multicenter study conducted in community pharmacies, which surveyed T2DM patients treated for at least 3 months. RESULTS: Overall, 233 pharmacies recruited 1890 patients (males: 50.6%) with mean 67.1 years. On average, participants reported having diabetes for 11.8 years. A total of 86.9% had at least one chronic illness or complication of diabetes, and 76.8% were usually followed in the primary care setting. Fifty eight percent were treated without a secretagogue or insulin. Overall prevalence of mild to moderate hypoglycemic episodes in the 3 months prior to recruitment was 17.8%. A 3.13% prevalence of severe hypoglycemia was observed in the last 12 months. Results suggested that men and patients on antihyperglycemic therapies excluding secretagogues or insulin were less likely to have mild to moderate hypoglycemic episodes. CONCLUSIONS: Mild to moderate hypoglycemic episodes were commonly reported, and factors like type of antihyperglycemic therapy, duration of disease and due complications may contribute. Almost half of episodes were not reported. Such factors should be considered in T2DM management.

The place of DPP-4 inhibitors in the treatment algorithm of diabetes type 2: a systematic review of cost-effectiveness studies.

OBJECTIVE: To conduct a systematic review of cost-effectiveness, cost-utility, and cost-benefit studies of DPP-4 inhibitors for diabetes treatment versus other antidiabetics. METHODS: Three investigators searched the CRD York, Tufts CEA Registry, and MEDLINE databases through 2015. We reviewed all potentially relevant titles and abstracts, and screened full-text articles, according to inclusion criteria. We established a quality score for each study based on a 35-item list. RESULTS: A total of 295 studies were identified, of which 20 were included. The average quality score was 0.720 on a 0-1 scale. All studies were performed in high- and middle-income countries, using a 3rd-party payer perspective and randomized clinical trials to measure effectiveness. Sitagliptin, saxagliptin and vildagliptin had an ICER below 25,000 €/QALY, as second-line and as add-ons to metformin, in comparison to sulfonylureas. When compared with sitagliptin, liraglutide (GLP-1 receptor agonist) had an ICER of up to 22,724 €/QALY for the 1.2-mg dosage, and up to 32,869 €/QALY for the 1.8-mg dosage. Insulin glargine was dominant when compared with sitagliptin. CONCLUSIONS: According to the WHO threshold applied to the country and year of each study, DPP-4 inhibitors were highly cost-effective as second-line, as add-ons to metformin, in comparison with sulfonylureas. More recent therapies (GLP-1 receptor agonists and insulin glargine) were highly cost-effective in comparison to DPP-4 inhibitors. These results were obtained, however, on the basis of a limited number of studies, relying on the same few clinical trials, and financed by manufacturers. Further independent research is needed to confirm these findings.