What is happening with not recommended drugs for dementia in Argentina? Prescription patterns and direct costs analysis.

OBJECTIVES: The only recommended pharmacological treatments for specific dementias are donepezil, galantamine, rivastigmine, and memantine (recommended drugs, RD). However, other drugs without recommendations (not recommended drugs, NRD) are often used to treat patients with cognitive impairment (CI) in Argentina. The INSSJyP is the largest health insurance in Argentina. The objective of this study is to analyze the prescription pattern, cost, and implications of NRD used for the treatment of CI in the INSSJyP. MATERIALS: This is a retrospective, population-based study of the INSSJyP outpatients' prescriptions database for drugs usually prescribed for CI during 2015. These data were compared with the same database in 2009. The number of "prescriptions" always refers to dispensed packages. RESULTS: A total of 3 255 438 packages of drugs usually indicated for CI were prescribed during 2015: 1 912 476 packages of RD (59%) and 1 342 962 packages of NRD (41%).Comparing the results with those obtained in 2009, there is a 148% gross increase in the prescription of both RD and NRD for CI, although the rates/1000 affiliates/year show a lesser rise for NRD (70.1%) compared to RD (103.9 %).The expenditure on CI drugs prescribed during 2015 was 77 million USD. NRD cost represented approximately 20 million USD. CONCLUSION: Inappropriate drug use increases health costs in developing countries. We found a high number of patients with a probable diagnosis of CI treated with NRD. It is extremely relevant that all the healthcare professionals can update their knowledge and modify behavioral insights about appropriate prescription for specific dementias.

[Psychotropic drugs prescription to elderly people in the national institute of social services for retirees and pensioners of argentina (PAMI)]. / Prescripción de psicofármacos a personas mayores en el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados de Argentina (PAMI).

OBJECTIVE: To analyze the prescribing pattern of psychotropic drugs to affiliates over 60 years of age at the National Institute of Social Services for Retirees and Pensioners of Argentina (PAMI). MATERIALS AND METHODS: We conducted a retrospective study of the at the National Institute of Social Services for Retirees and Pensioners of Argentina (PAMI) database on the population over 60 years of age who received at least one psychotropic drug during 2016. RESULTS: During the year 2016, 30% of the population over 60 years of age received the prescription of at least one psychotropic drug. There was a greater prescription of psychotropic drugs to women than to men (75.3% vs. 24.7%). Of the drugs prescribed, 67% were benzodiazepines, 20% were antidepressants, 9% were antipsychotics and 4% were non-benzodiazepine hypnotics. 54% of the drugs prescribed were clonazepam and alprazolam. 21% of the population received three or more prescriptions during the period studied. There was a relatively greater prescription of psychotropic drugs in the population of 75 years old or older. CONCLUSIONS: Taking into account the risks of adverse effects, interactions and the inclusion of some of these drugs among those that should not be prescribed among older adults, the high prescription rate of some of these drugs is alarming. It is necessary to develop strategies among general practitioners, specialists and also among the general population in order to reduce the prescription of psychotropic drugs.

[Adrenal insufficiency in cirrhotic patients]. / Insuficiencia suprarrenal relativa en pacientes cirróticos.

Relative adrenal insufficiency (RAI) is a common finding in cirrhotic patients with severe sepsis, and increased mortality. Its significance is unknown in stable conditions. The aim of this study was to evaluate the prevalence of RAI in stable cirrhotic patients at different stages of the disease. Also, the impact of RAI on the survival was evaluated and basal cortisol levels between plasma and saliva was correlated in control subjects and cirrhotic patients. Forty seven ambulatory patients and 16 control subjects were studied. RAI was defined as a serum cortisol increase of less than 9 υg/dl from baseline after the stimulation with 250 mg of synthetic ACTH. Twenty two had Child-Pugh = 8 and 25 = 9. The prevalence of RAI in patients with stable cirrhosis was 22%. A higher incidence of RAI was observed in patients with a Child-Pugh = 9 (8/32) than in those with = 8 (3/13, p < 0.05). A correlation between salivary cortisol and basal plasma cortisol (r = 0.6, p < 0.0004) was observed. Finally, survival at 1 year (97%) and 3 years (91%) was significantly higher without RAI than those who developed this complication (79% and 51%, p < 0.05, respectively). In summary, the prevalence of RAI is frequent in patients with stable cirrhosis and that it is related to the severity of liver diseaseand increased mortality.

Meal ingestion markedly increases liver stiffness suggesting the need for liver stiffness determination in fasting conditions.

INTRODUCTION: The introduction of noninvasive liver stiffness (LS) determination has heralded a new stage in the diagnosis and treatment of liver fibrosis. AIM: We evaluated the effect of food intake on LS in patients with different degrees of liver disease. PATIENTS AND METHODS: We evaluated 24 patients (F≤1, n=11 and F> 1, n=13). LS (Fibroscan®) and portal blood flow (PBF) (Doppler ultrasound) were studied before and 30min after ingestion of a standard liquid meal. RESULTS: Food intake increased PBF (51±10%, p<0.001). Splanchnic hyperemia was accompanied by a significant rise in LS (from 7.8±3.3 to 10.3±4.1kPa, p<0.001). These increases were similar in patients with minimal fibrosis(F≤1) and in those with more advanced fibrosis or cirrhosis (F>1). Hemodynamic and LS values returned to baseline pre-meal levels within 2hours. CONCLUSION: LS increases markedly after ingestion of a standard meal, irrespective of the degree of fibrosis. Our results strongly suggest that LS should be measured in fasting conditions.

[De novo malignant tumors following liver transplantation. A single-center experience in Argentina]. / Tumores malignos de novo en el trasplante hepático. Experiencia de un centro en la Argentina.

The aim of the present study was to evaluate the incidence and clinical features of de novo tumors in patients undergoing liver transplantation in our center as well as to assess survival. We retrospectively analyzed 168 liver transplantations (159 patients) performed from May 2006 to May 2014. The incidence of de novo tumors was 7.5% (n = 12). The mean age at diagnosis was 63 ± 7 years. The most frequent neoplasms were non melanoma skin tumors and adenocarcinomas. Fifty percent of the tumors developed in the second and third year after transplantation. Type of immunosuppression did not influence tumoral type, although most patients receive tacrolimus in combination with mycofenolate and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 25 ± 29 months (range 0-76) and the mortality was 41%. The actuarial probability of survival at 1 and 5 years was 83 and 55%, respectively. De novo tumors are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow up of these patients is essential for early diagnosis.

Changing etiologies and outcomes of acute liver failure: perspectives from 6 transplant centers in Argentina.

There is significant geographic variation in the etiologies and prognoses of acute liver failure (ALF). The aims of the present study were to determine the causes and short-term outcomes of ALF in Argentina, to evaluate the performance of prognostic criteria, and to identify clinical prognostic factors of death. We performed a retrospective analysis of 154 adult patients with ALF who were admitted to 6 liver transplantation (LT) programs between June 2005 and December 2011. The most frequent causes of ALF were viral hepatitis B (46 patients or 30%), autoimmune hepatitis (AIH; 40 patients or 26%), and indeterminate causes (40 patients or 26%). No acetaminophen (ACM) overdose was reported. One hundred and twenty one patients (78%) were included on the waiting list, and LT was performed for 83 patients (54%). Overall survival rate is now corected to 73%. Multivariate logistic regression identified 2 independent variables associated with adverse outcomes on admission: a Model for End-Stage Liver Disease (MELD) score ≥ 29 and an encephalopathy grade ≥ 3. In a direct comparison using a receiving operating characteristic curve analysis, the MELD score [C statistic = 0.830, 95% confidence interval (CI) = 0.73-0.93] had better prognostic accuracy for predicting outcomes than the Clichy criteria (C statistic = 0.719, 95% CI = 0.58-0.85) or the King's College criteria (C statistic = 0.631, 95% CI = 0.49-0.77). In conclusion, hepatitis B and AIH were the most frequent causes of fulminant hepatic failure in our series, and no cases of ACM overdosing were identified. A MELD score ≥ 29 and an encephalopathy grade ≥ 3 at admission were associated with death. The MELD score at admission showed the highest prognostic accuracy.

Fibrosis progression in maintenance liver transplant patients with hepatitis C recurrence: a randomised study of everolimus vs. calcineurin inhibitors.

BACKGROUND & AIMS: Robust clinical data evaluating fibrosis progression in hepatitis C virus (HCV) liver transplant patients receiving an mTOR inhibitor vs. calcineurin inhibitor (CNI) are lacking. To evaluate fibrosis progression in maintenance liver transplant patients receiving everolimus- or CNI-based immunosuppression. METHODS: In a randomised, multicentre, open-label study, 43 maintenance liver transplant patients with recurrent HCV infection were randomised to continue CNI-based immunosuppression or switch to everolimus. RESULTS: For patients with biopsy data at month 12, mean Ishak-Knodell fibrosis score at baseline was 2.6 ± 0.9 (n = 14) with everolimus vs. 1.9 ± 1.1 (n = 18) with CNI (P = 0.043), and 1.9 ± 1.2 vs. 2.2 ± 1.3 at month 12. Ishak-Knodell fibrosis score decreased from baseline to month 12 by a mean of -0.7 ± 1.1 with everolimus, but increased by 0.2 ± 1.2 with CNI (P = 0.046). No acute rejection or graft losses occurred up to month 12. Estimated GFR at month 12 was 65.6 ml/min/1.73 m² with everolimus and 62.2 ml/min/1.73 m² with CNI [mean difference 3.4 ml/min/1.73 m² compared to CNI control group, 95% CI -4.9, 11.8 ml/min/1.73 m², P = 0.411 (analysis of covariance adjusting for baseline GFR)]. Adverse events occurred in 95.5% of everolimus patients and 71.4% of CNI patients (serious adverse events 31.8% and 0.0%, respectively). Adverse events led to everolimus discontinuation in five patients (22.7%). CONCLUSIONS: This exploratory study suggests that conversion from CNI to everolimus reduces progression of liver fibrosis, and preserves renal function without jeopardising efficacy in liver transplant recipients with recurrent HCV, but is associated with a higher incidence of adverse events and serious adverse events. These preliminary findings merit examination in a larger trial.

Latin American Association for the Study of the Liver (LAASL) clinical practice guidelines: management of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

An unreported case of pancreatic panniculitis in a liver transplant patient.

Pancreatic panniculitis is an uncommon condition that can occur in association with pancreatic disease. Most of the cases reported to date were associated with acute or chronic pancreatitis and pancreas cancer. Recently, development has been described in kidney transplant patients and secondarily to allograft pancreatitis in a pancreas-kidney transplant recipient. Both findings suggest that immunological processes may be involved in the pathogenesis of this entity. We report for the first time a case of acute pancreatitis associated with pancreatic panniculitis in a patient who underwent a liver transplant 10 months before. A 69-year-old man with a history of epigastric pain of a few days of evolution was presented with painful subcutaneous nodules on both legs. Blood chemistry showed raised serum amylase and lipase levels. Ultrasonography and multislice CT scan were suggestive of an acute pancreatitis. A skin biopsy showed typical features of pancreatic panniculitis which included lobular panniculitis with lipocyte degeneration with ghost cells. The administration of octreotide resulted in both a rapid improvement of symptoms and a disappearance of skin lesions. Liver transplant specialists should be aware that the pancreatic panniculitis could be a manifestation ofpancreas disease in patients who have undergone l ver transplantation.

[Cost analysis of liver transplantation in a community hospital: association with the Model for End-stage Liver Disease, a prognostic index to prioritize the most severe patients]. / Análisis del coste del trasplante hepático en un hospital de la comunidad: su relación con el Model for End-stage Liver Disease, un índice pronóstico que prioriza al paciente más grave.

INTRODUCTION: The aim of the present study was to investigate the impact of the Model for End-stage Liver Disease (MELD) on transplantation costs. MATERIAL AND METHODS: We included all patients who received a liver transplant for end-stage liver disease between 2006 and 2010. The study period encompassed the day of transplantation until hospital discharge. The patients were classified into two groups: those with a MELD score of 6-19 and those with a score of 20-40. RESULTS: The mean MELD score at transplantation was 19.2±7.0 (mean±SD). The mean cost per procedure in the study period was USD 33,461 per patient (range 21,795-104,629). The cost of transplantation was USD 30,493±8,825 in patients with a MELD score of 6-19 and was USD 36,506±15,833 in those with a score of 20-40; this difference was statistically significant (P=.04). In a stepwise logistic regression analysis, the only independent predictor of high cost was having a MELD score of 20 (OR 11.8; CI 1.6-87). In the linear regression model, the most important predictor of cost was the length of hospital stay (r(2)=43%). DISCUSSION: Our results demonstrate that the MELD score directly affects transplantation costs. We suggest that reimbursement systems compensate the distinct financing bodies according to the severity of the underlying disease, evaluated with the MELD.

[Efficacy of the association of a single dose of hepatitis B hyperimmune gammaglobulin and entecavir in the prophylaxis of hepatitis B after liver transplantation: experience of a single center in Argentina]. / Eficacia de la asociación de una sola dosis de gamaglobulina hiperinmune anti-hepatitis B más entecavir en la profilaxis de la hepatitis B después del trasplante hepático: experiencia de un centro en la Argentina.

The present study reports the effectiveness of the association of a single dose of hepatitis B immunoglobulin (HBIg) associated to entecavir in the prophylaxis of hepatitis B in patients who have undergone liver transplantation. Six patients that had been transplanted because of hepatitis B liver disease were retrospectively evaluated. Three of them developed non-oncological complications related to liver cirrhosis, two had hepatocellular carcinoma and another one had fulminant HBV hepatitis. The mean follow-up was 22 months (range: 7-52 months). The 6 patients received entecavir as prophylactic treatment before transplantation. The pretransplant viral load was undetectable in all patients. HBsAg seroconversion was observed in four of the six patients. Three patients died during follow-up, two because of recurrent hepatocellular carcinoma, none of them had detectable HBV serum viral load. In a small series of patients we could demonstrate that a regimen with a single dose of gamma globulin entecavir is effective in the post-transplant management of patients with liver disease associated with HBV. Future studies will be able to demonstrate the effectiveness of specific gamma globulin-free regimens.

Is it safe to use a liver graft from a Chagas disease-seropositive donor in a human immunodeficiency virus-positive recipient? A case report addressing a novel challenge in liver transplantation.

This is the first report presenting a human immunodeficiency virus (HIV)-positive patient with fulminant hepatic failure receiving a liver graft from a Chagas disease-seropositive deceased donor. We describe the history of a 38-year-old HIV-positive female patient who developed fulminant hepatic failure of an autoimmune etiology with rapid deterioration of her clinical status and secondary multiorgan failure and, therefore, needed emergency liver transplantation (LT) as a lifesaving procedure. Because of the scarcity of organs and the high mortality rate for emergency status patients on the LT waiting list, we decided to accept a Chagas disease-seropositive deceased donor liver graft for this immunocompromised Chagas disease-seronegative patient. The recipient had a rapid postoperative recovery and was discharged on postoperative day 9 without prophylactic treatment for Chagas disease. Fifteen months after LT, she was still alive and had never experienced seroconversion on periodic screening tests for Chagas detection. Although there is an inherent risk of acute Chagas disease developing in seronegative recipients, our report suggests that these infected organs can be safely used as a lifesaving strategy for HIV patients with a high need for LT.

[Usefulness of transient elastography (Fibroscan®) in the assessment of fibrosis in patients with chronic liver disease]. / Utilidad de la elastografia de transición (Fibroscan®) en la evaluación de la fibrosis hepática en pacientes con hepatopatía crónica.

The prognosis and management of chronic liver disease largely depends on the extent and progression of liver fibrosis. Unfortunately, liver biopsy, an invasive and painful technique with several limitations, continues to be the gold standard for the staging and grading of fibrosis. Therefore, accurate noninvasive tests for liver injury are urgently needed. During the last years, transient elastography (Fibroscan®) has been proposed for the assessment of hepatic fibrosis in patients with chronic liver disease, by measuring liver stiffness. The aim of this study was to evaluate the effectiveness, objectivity and safety of this technique. We included 68 patients who underwent a liver biopsy in the last 18 months with a wide spectrum of chronic liver diseases. All procedures as well as the liver biopsies according to the METAVIR scoring system were analyzed by the same sonographer and the same specialist in pathology, respectively. Median value of stiffness with none or mild fibrosis (F0 and FI), and severe fibrosis or cirrhosis (F3 and F4) was 6.8 ± 3.0 kPa and 21.0 ± 15.1 kPa, respectively, with a significant difference between them (p < 0.01). The areas under the receiver operating characteristic curves showed the optimal liver stiffness cut-off values for each group. We found also a positive correlation between liver stiffness found by transient elastography and fibrosis stage on biopsy in all patients, independently of the liver disease etiology. Fibroscan® is an easy, quick to perform and safe non-invasive method, reliable for assessing liver fibrosis.

[Liver trasplantation for the treatment of non-resectable metastases of neuroendocrine tumors: first report in Argentina]. / Trasplante hepático como tratamiento de las metástasis de tumores neuroendócrinos: primer reporte en la Argentina.

Neuroendocrine tumors are uncommon cancers characterized by a slow grow rate. Unresectable liver metastases are the main cause of death in patients with these tumors. This is the first Argentine report of a liver transplantation as an indication for the treatment of unresectable liver metastases from a pancreatic neuroendocrine tumor. We present a 48-year-old woman with diagnosis of a pancreatic neuroendocrine tumor with multiple bilobar unresectable liver metastases. A splenopancreatectomy was performed after a complete staging revealed absence of extrahepatic disease. Six months later, a follow-up performed with thoracoabdominal CT scan and octreo-scan was consistent with no tumor recurrence or extrahepatic disease. As the huge hepatomegaly caused a notorius deterioration in the patient's quality of life, we decided to include her in the waiting list for liver transplantation. Priority points were requested to the MELD (model for end stage liver disease) Exceptions Experts Committee with a positive response. Twelve months after the primary surgery, with a MELD score of 23 points, a deceased donor liver transplantation was performed without evidence at that moment of residual disease. Eighteen months after liver transplantation, the patient required the surgical repair of a stenosis in the biliary anastomosis. At the surgery peritoneal tumor recurrence was diagnosed. Now, 24 months after liver transplantation the patient has an excellent quality of life and a well functioning graft. We report this case of a liver transplantation as an indication for the treatment of liver metastases from a neuroendocrine tumor and we review the literature on this controversial issue.

[Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017]. / Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017.

In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.

En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

Rescue policy for discarded liver grafts: a single-centre experience of transplanting livers 'that nobody wants'.

BACKGROUND: There is a worldwide need to expand the donor liver pool. We report a consecutive series of elective candidates for liver transplantation (LT) who received 'livers that nobody wants' (LNWs) in Argentina. METHODS: Between 2006 and 2009, outcomes for patients who received LNWs were analysed and compared with outcomes for a control group. To be defined as an LNW, an organ is required to fulfil two criteria. Firstly, each liver must be officially offered and refused more than 30 times; secondly, the liver must be refused by at least 50% of the LT programmes in our country before our programme can accept it. Principal endpoints were primary graft non-function (PNF), mortality, and graft and patient survival. RESULTS: We transplanted 26 LNWs that had been discarded by a median of 12 centres. A total of 2666 reasons for refusal had been registered. These included poor donor status (n= 1980), followed by LT centre (n= 398) or recipient (n= 288) conditions. Incidences of PNF (3.8% vs. 4.0%), in-hospital mortality (3.8% vs. 8.0%), 1-year patient (84% vs. 84%) and graft (84% vs. 80%) survival were equal in the LNW and control groups. CONCLUSIONS: Transplantable livers are unnecessarily discarded by the transplant community. External and internal supervision of the activity of each LT programme is urgently needed to guarantee high standards of excellence.

[Liver transplantation during pregnancy in a patient with acute liver failure]. / Trasplante hepático durante el embarazo en una paciente con insuficiencia hepática aguda grave.

Liver transplantation is the best therapeutic approach in patients with acute liver failure. This clinical presentation during pregnancy is an unusual and dramatic event. We report the case of a 18 year-old woman with cryptogenic acute liver failure who underwent successful orthotopic liver transplantation at 20 weeks of pregnancy. Both outcomes were analyzed. Fetal death was observed within 48 hours after liver transplant. After six months of follow-up, the patient is doing well. This case illustrates the challenge of treating acute liver failure during pregnancy and demonstrates that liver transplantation is a feasible therapeutic option for treatment of patient with this condition.

Effect of a Social Norm Email Feedback Program on the Unnecessary Prescription of Nimodipine in Ambulatory Care of Older Adults: A Randomized Clinical Trial.

Importance: Nimodipine is a highly prescribed drug for the treatment of cognitive impairment and dementia in Argentina. There is little evidence to support the use of nimodipine for cognitive impairment and dementia. Objective: To test the effectiveness of a behavioral intervention based on social norm feedback to reduce prescription of nimodipine for cognitive impairment in Argentina. Design, Setting, and Participants: This pragmatic parallel-group randomized clinical trial included 2 arms with a 1:1 allocation ratio. General practitioner physicians in the national health care system for older adults in Argentina (INSSJP-PAMI) with history of high nimodipine prescription rate were enrolled. The study was conducted from May 2019 to October 2019, and data were analyzed from November 2019 to February 2020. Interventions: The treatment group received 2 emails with evidence-based information about nimodipine plus the individual's level of nimodipine prescription compared with their peers. The control group received 2 emails with general information about the risks of overprescription in older adults. Main Outcomes and Measures: The primary outcome was the cumulative number of nimodipine prescriptions per 1000 prescriptions of all drugs made by the targeted physicians during the 6 months of the study. Secondary outcomes included annual monetary savings attributable to the intervention and physicians' qualitative perceptions of the acceptability of the procedure. Results: Of 1811 physicians enrolled, 906 physicians (354 [39.1%] women; mean [SD] age, 57.10 [10.73] years) were randomized to treatment and 905 participants (331 [36.6%] women; mean [SD] age, 56.49 [10.47] years) to the control group. Physicians in the treatment group wrote a mean of 93.25 (95% CI, 89.27 to 97.24) prescriptions of nimodipine, compared with 98.99 (95% CI, 95.00 to 102.98) prescriptions among practitioners in the control group during the half-year of the intervention (mean difference, -5.73 [95% CI, -11.38 to -0.10] prescriptions; P = .046), which meant a 5.79% reduction. Regression analysis revealed a significant association of the group condition with number of prescriptions per 1000 total prescriptions when controlling for baseline prescriptions (B = -0.312 [95% CI, -0.465 to -0.160]; P < .001). The observed difference corresponds to a 4.48% reduction in nimodipine prescriptions per 1000 prescriptions of all drugs made by physicians in the treated group compared with the control group. Physicians who effectively opened the email in the treatment group (427 physicians [47.1%]) prescribed the drug 11.3% less compared with the control group (426 physicians) (mean difference, -10.78 [95% CI, -18.53 to -3.03] prescriptions; P = .006). Expenditures were 7.18% lower in the treatment group, resulting in an estimated annual net cost benefit of US $234 893.35 (95% CI, $225 565.35 to $237 112.30). Conclusions and Relevance: In this randomized clinical trial, the social norm email feedback program showed an effect on curbing the nonrecommended prescription of nimodipine. It was highly cost-effective and well accepted by participants. Trial Registration: ISRCTN.org identifier: ISRCTN17823729.

[Toxic hepatitis by consumption Herbalife products a case report]. / Hepatitis aguda asociada al consumo de Herbalife a propósito de un caso.

Toxic hepatitis by consumption Herbalife products is an affection poorly documented and with a great impact in the population due to their massive consumption. We present the case of a 63-years-old woman with probable diagnosis of toxic hepatitis secondary to the consumption of nutritional supplements Herbalife. The nutritional supplements based on natural ingredients are of massive consumption worldwide. Because they are recognized like innocuous and of non-controlled comercialization, they lack suitable controls. Although there are reported cases of hepatotoxicity and other side effects induced by these products, there is still not strong evidence to generate a positive reaction of the control organisms. We report a case of acute toxic hepatitis potencially due to the consumption of Herbalife.

Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017 / Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017

RESUMEN En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

ABSTRACT In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.