Stepwise Therapy Research Articles

Optimizing Pain Control During the Opioid Epidemic.

The current opioid crisis has raised awareness of the risks of misuse, addiction, and overdose with opioid prescribing for pain management in the perioperative and nonoperative care of surgical patients. Despite these risks, it is essential for surgical providers to provide safe and adequate functional pain control to enhance recovery. The purpose of this review is to outline the relevance of the US opioid crisis to surgical prescribing, describe strategies for opioid reduction using a stepwise therapy approach, and provide recommendations for improving the safety of opioid prescribing. Additional recommendations for risk assessment and naloxone coprescribing for high-risk patients are addressed.

Milestones in the discovery of Budd-Chiari syndrome.

In 1845, George Budd published a brief report regarding three patients who developed an obstruction of the hepatic veins. The condition has never been reported before, and was related to sepsis and alcoholism. Fifty-three years later, Hans Chiari postulated that syphilis was causing the obstruction of the hepatic veins, and enriched the debate with clinical and pathological correlations. Following the hypothesis on the 'phlebitis obliterans', several authors proposed other pathophysiological explanations including congenital causes, chronic trauma and exogenous toxins. RG Parker, in 1959, first recognized the relationship between obstruction of hepatic veins and thrombophilic conditions such as polycythaemia vera, pregnancy and hormonal therapy. Based on that, anticoagulant treatment was attempted, but with unsatisfactory outcome. We need to wait until the mid 1980s to see a widespread adoption of anticoagulants, with a consequent improvement of patients' survival. The fear of haemorrhagic events in patients with liver disease discouraged this therapeutic approach, and other surgical interventions (mainly port-systemic shunts) were conceived, but with high morbidity and mortality. The first liver transplantation in 1976 and the first trans-jugular intra-hepatic porto-systemic shunt in 1993 represented two major cornerstones in the management of Budd-Chiari syndrome (BCS). Such progresses allowed modifying the treatment of BCS until the modern concept of stepwise therapy. The present review thoroughly reviews the major landmarks in the discovery, treatment and clinical management of patients with BCS.

The Role of Steroids and NSAIDs in Prevention and Treatment of Postsurgical Cystoid Macular Edema.

Pseudophakic cystoid macular edema (PCME) remains one of the most common visionthreatening complication of phacoemulsification cataract surgery (PCS). Pharmacological therapy is the current mainstay of both prophylaxis, and treatment of PCME in patients undergoing PCS. We aimed to review pharmacological treatment options for PCME, which primarily include topical steroids, topical nonsteroidal antiinflammatory drugs (NSAIDS), periocular and intravitreal steroids, as well as anti-vascular endothelial growth factor therapy. The PubMed and Web Of Science web platforms were used to find relevant studies using the following keywords: cataract surgery, phacoemulsification, cystoid macular edema, and pseudophakic cystoid macular edema. Of articles retrieved by this method, all publications in English and abstracts of non-English publications were reviewed. Other studies were also considered as a potential source of information when referenced in relevant articles. The search revealed 193 publications. Finally 82 articles dated from 1974 to 2018 were assessed as significant and analyzed. Based on the current literature, we found that corticosteroids remain the mainstay of PCME prophylaxis in uncomplicated cataract surgery, while it is still unclear if NSAID can offer additional benefits. In patients at risk for PCME development, periocular subconjunctival injection of triamcinolone acetonide may prevent PCME development. For PCME treatment the authors recommend a stepwise therapy: initial topical steroids and adjuvant NSAIDs, followed by additional posterior sub-Tenon or retrobulbar corticosteroids in moderate PCME, and intravitreal corticosteroids in recalcitrant PCME. Intravitreal anti-vascular endothelial growth factor agents may be considered in patients unresponsive to steroid therapy at risk of elevated intraocular pressure, and with comorbid macular disease. Therapy with topical corticosteroids and NSAIDs is the mainstay of PCME prophylaxis and treatment, however, periocular and intravitreal steroids should be considered in refractory cases.

Analysis of antiviral use efficiency criteria in the complex pharmacotherapy of community acquired pneumonia

According to modern view, bacterial pathogens are the leading and most common cause of community-acquired pneumonia (CAP), but at the same time the results of numerous microbiological studies conducted in recent years showed that viruses confidently play the next leading role of CAP causes. Today, antiviral therapy is successfully used within the complex therapy of respiratory diseases, which allows reduction of the disease severity and minimizes the risk of complications. The main requirements for the antiviral drug are fully responsive to the new antiviral drug vitaglutam, the active component of which is pentanedioic acid imidazolyl ethanamide, is a low molecular weight compound, an analogue of the natural peptidoamine.
 The aim of the work. Mathematical modeling and analysis of clinical and laboratory indicators dynamics of CAP with additional antiviral pharmacotherapy based on pentanedioic acid imidazolyl ethanamide.
 In the study, it was used retrospective data of 106 patients with mild form of CAP of viral and bacterial etiology. Patients were randomly divided into two groups. In the 1st main group (50 patients), antibacterial therapy was combined with the antiviral drug vitaglutam. Analysis of antiviral therapy efficiency was provided by grouping of patients and determination of their distribution by gradations of clinical and laboratory indicators, as well as the construction of a mathematical model of their dynamics.
 According to modeling results, the rate of body temperature normalization, which was higher in patients taking vitaglutam, was a clear criterion for the efficiency of antiviral therapy. With additional antiviral therapy, the dynamics of sputum in the lungs was less intense. Positive clinical changes were accompanied by an improvement in the clinical blood analysis indicators, namely, more significant was the dynamics of ESR decrease. At the same time, dynamics of leukocytes number in patients’ blood was approximately the same in both groups.
 Analysis of dynamics of clinical and laboratory indicators using the proposed mathematical model suggests that additional prescription of vitaglutam to empirical stepwise antibiotic therapy can significantly reduce the time to achieve clinical and laboratory results of treatment of patients with CAP of viral and bacterial etiology.

Local suture ligation-assisted percutaneous sclerotherapy for Kasabach-Merritt phenomenon-associated kaposiform haemangioendothelioma.

Kaposiform haemangioendotheliomas (KHEs) complicated by the Kasabach-Merritt phenomenon (KMP) are rare and severe neoplastic lesions often associated with locally aggressive disease, consumption coagulopathy and high mortality rates. Current regimens have yet to achieve a satisfactory therapeutic effect. Thus, an effective and minimally invasive approach for treating complex KHE/KMP cases is necessary for clinical management. The present case series describes patients with KHE/KMP who underwent local suture ligation-assisted percutaneous sclerotherapy to minimise surgical trauma and ensure effective treatment. Between September 2015 and September 2017, 3 consecutive patients with KHE/KMP underwent staged local suture ligation-assisted percutaneous sclerotherapy. Of these patients, 2 presented with medical histories of corticosteroid treatment with unsatisfactory outcomes. The patients underwent a stepwise synthetic serial therapy programme consisting of percutaneous sclerotherapy and adjunctive pharmacotherapy accompanied by a suture ligation procedure. Clinical, radiological, pathological and laboratory data were analysed to evaluate the outcomes of the therapy. All patients were successfully managed with the proposed procedure. Significant relief of clinical symptoms and improvements in haematological indicators were achieved. No recurrence or complications were observed during regular follow-up (4, 19 and 28 months). In conclusion, local suture ligation-assisted percutaneous sclerotherapy was demonstrated to be a safe and effective treatment for KHE/KMP, being minimally invasive, involving simple manipulation and providing a clear treatment benefit in certain cases. Further studies involving larger sample sizes are required to thoroughly evaluate the procedure, which can potentially be used as a novel therapeutic option for KHE/KMP treatment.

Rational stage hormonal and nonhormonal local therapy of psoriasis

Objective — to investigate the clinical efficacy of nonhormonal cream Рsory Active which includes a number of natural components in the complex stepwise local therapy of patients with psoriasis with limited and disseminated forms of skin lesions compared with local monotherapy with only corticosteroid agents of different strength.Materials and methods. We observed 37 patients with psoriasis of limited and disseminated forms of lesions at the stage of progression or at a stationary stage of the skin psoriatic process. The age of patients ranged from 19 to 68 years. There were 21 men and 16 women. The duration of psoriasis in the examined patients ranged from 2 years to 46 years. PASI index was determined in patients with consideration of the clinical and morphological picture of cutaneous psoriatic lesions. The study involved patients with psoriasis with PASI index of 19 to 50 points. All examined patients with psoriasis were divided into 2 equivalent groups. The first (main) group included 19 patients, and the second (comparative) group — 18 patients. The tactics of our local step­by­step therapy for psoriasis patients of the first (main) group included initially a short­term use (5—10 days) of one of the topical corticosteroid agents of very strong or strong effects, followed by the appointment of one of the topical corticosteroids of moderate or weak action for four to six weeks.Results and discussion. At the beginning of treatment, according to the clinical and morphological pattern of cutaneous psoriatic lesions, PASI index in patients with psoriasis of the first (main) group averaged 22.3 points, and in the patients of the second (comparative) group — 21.9 points. After the completion of the local therapy, that is, in 6—7 weeks from its beginning in patients of the first group, the PASI index averaged 8.1 points, and in the second group — 9.2 points. Thus, in patients with psoriasis of both groups, after local therapy courses, there was a significant, almost identical regression of cutaneous psoriatic rash.Conclusions. The use of a stepwise scheme of local therapy in patients with psoriasis of limited and disseminated forms of skin lesions by means of short­term (individualized) administration within five to ten days of one of the topical corticosteroids of very strong or strong action with subsequent use within four to five weeks of nonhormonal cream Psory Active containing a number of natural components, is quite effective (according to PASI index) and more reasonable in comparison with the use of only topical corticosteroid monotherapy.

Step-wise Drug Therapy for Comorbid Bipolar and Obsessive–Compulsive Disorders

Step-wise Drug Therapy for Comorbid Bipolar and Obsessive–Compulsive Disorders

Efficacy and tolerability of novel triple combination therapy in drug-naïve patients with type 2 diabetes from the TRIPLE-AXEL trial: protocol for an open-label randomised controlled trial

IntroductionPatients with type 2 diabetes are at risk of microvascular and macrovascular complications. Intensive glycaemic control, especially in patients with short duration of diabetes, is the mainstay of management of...

Triple Therapy for COPD Patients

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend stepwise therapy for patients with chronic obstructive pulmonary

Tiotropium for the Treatment of Asthma: Patient Selection and Perspectives.

Asthma is a chronic disease of airway inflammation with a large global burden. Despite established, guideline-based stepwise therapy, a significant proportion of patients remain symptomatic and poorly controlled. As such, there is a need for additional safe, effective, convenient, and cost-effective therapies that can be broadly applied across a range of asthma phenotypes. Tiotropium is a long-acting muscarinic antagonist (LAMA) that leads to bronchodilation by blocking endogenous acetylcholine receptors in the airways. Tiotropium has long been approved for the treatment of chronic obstructive pulmonary disease, and it has recently been recognized for its safety and efficacy in improving lung function and controlling asthma. Evidence from several Phase III trials in the adult and paediatric population has shown that tiotropium is well tolerated and significantly improves a range of endpoints as an add-on treatment to ICS therapy, regardless of baseline characteristics and clinical phenotypes. Consequently, regulatory authorities worldwide have recently licensed tiotropium as the only LAMA approved for the treatment of asthma. This review provides an overview of safety and efficacy data and discusses the use of tiotropium in patients across the range of asthma severities, ages, and phenotypes.

Management of Itch in Atopic Dermatitis.

Atopic dermatitis (AD) is the most common itchy dermatosis that affects millions of children and adults worldwide. Chronic itch in this condition has significant impact on measures of quality of life, such as sleep. Treating itch in AD has been challenging for decades, but new drugs have emerged in the last year with significant anti-pruritic effect. The optimal treatment regimen for atopic itch addresses barrier dysfunction, inflammation, neural hypersensitivity, and the itch-scratch cycle. Topical moisturizers remain the foundation of treatment and should be used by all patients with AD-associated pruritus. Step-wise therapy, from topical anti-inflammatory creams to systemic monoclonal antibodies and immunosuppressants, is recommended. There are multiple adjuvant therapies that can be used, especially to target itch in the setting of minimal skin inflammation. Finally, patient education, sleep management, and stress relief are important components to optimize outcomes. This review assesses the latest advances and treatment recommendations for pruritus in AD. Finally, suggested therapeutic ladders and emerging treatments are discussed.

Initiating therapy in patients newly diagnosed with type 2 diabetes: Combination therapy vs a stepwise approach.

There is clear evidence that achieving glycaemic targets reduces the risk of developing complications as a result of type 2 diabetes (T2D). Many patients, however, continue to have suboptimal glycaemic control because of issues that include unclear advice on how to achieve these targets as well as clinical inertia. The two management approaches recommended for patients newly diagnosed with T2D are stepwise and combination therapy, each of which has advantages and disadvantages. Stepwise therapy may result in good patient adherence and allow greater individualization of therapy, and minimization of side effects and cost, and so may be appropriate for patients who are closer to goal. Stepwise therapy, however, may also lead to frequent delays in achieving glycaemic goals and longer exposure to hyperglycaemia. Combination therapy, which is now emerging as an important therapy option, has a number of potential advantages over stepwise therapy, including reduction in clinical inertia and earlier and more frequent achievement of glycated haemoglobin goals by targeting multiple pathogenic mechanisms simultaneously, which may more effectively delay disease progression. Compared with stepwise therapy, the disadvantages of combination therapy include reduced patient adherence resulting from complex, multi-drug regimens, difficulty determining the cause of poor efficacy and/or side effects, patient refusal to accept disease, and higher cost. Fixed-dose and fixed-ratio combinations are novel therapeutic approaches which may help address several issues of treatment complexity and patient burden associated with combination therapy comprising individual drugs. The choice of which drugs to administer and the decision to use stepwise vs combination therapy, however, should always be made on an individualized basis.

Very Poorly Controlled Asthma in Urban Minority Children: Lessons Learned

Very poorly controlled (VPC) asthma in children is associated with ongoing acute exacerbations but factors associated with VPC are understudied. To examine the risk factors associated with VPC asthma in urban minority children. This descriptive study examined asthma control levels (well-controlled [WC], not well-controlled [NWC], and VPC) at baseline and 6 months in children participating in an ongoing randomized controlled trial of an emergency department/home environmental control intervention. Data collection occurred during the index emergency department visit and included allergen-specific IgE and salivary cotinine testing and caregiver interview of sociodemographic and child health characteristics. Follow-up data were collected at 6 months. Unadjusted analyses examined the association of sociodemographic and health characteristics by level of asthma control. Multivariate analysis tested significant factors associated with VPC asthma at 6 months. At baseline most children were categorized with VPC asthma (WC, 0%; NWC, 47%; VPC, 53%) and rates of VPC minimally improved at 6 months (WC, 13%; NWC, 41%; VPC, 46%). Risk for VPC asthma was twice as likely in children with allergic rhinitis (odds ratio [OR], 2.42), having 2 or more primary care provider asthma visits within the past 3 months (OR, 2.77), or caregiver worry about medication side effects (OR, 2.13) and 3 to 4 times more likely when asthma control was assessed during the fall or spring season (OR: fall, 3.32; spring, 4.14). Improving asthma control in low-income, high-risk children with VPC asthma requires treatment of comorbidities, attention to caregiver medication beliefs, and adept use of stepwise therapy.

Use of stepwise lactate kinetics-oriented hemodynamic therapy could improve the clinical outcomes of patients with sepsis-associated hyperlactatemia

BackgroundSetting lactate kinetics at >30% might improve the clinical outcomes of patients with sepsis-associated hyperlactatemia. The aim of this study was to explore the outcome benefits of stepwise lactate kinetics vs central venous oxygen saturation (ScvO2)-oriented hemodynamic therapy at 6 h as the protocol goal during early resuscitation.MethodsThe relevant parameters and adverse events after different targets in 360 randomly assigned patients with sepsis-associated hyperlactatemia were recorded and compared.ResultsHeart rate (HR) at 48 h in the ScvO2 group was higher than in the lactate kinetics group (105 ± 19 bpm vs 99 ± 20 bpm, P = 0.040). The liquid balance at 4 h, 12 h, and 24 h in the lactate kinetics group was larger than in the ScvO2 group (1535 (1271–1778) ml vs 826 (631–1219) ml, P < 0.001; 1688 (1173–1923) ml vs 1277 (962 − 1588) ml, P <0.001; and 1510 (904–2087) ml vs 1236 (740–1808) ml, P = 0.005), respectively. Mortality was higher in the ScvO2 group (27.9% vs 18.3%, P = 0.033), but there was no significant difference between the two groups in the length of stay in the ICU or mechanical ventilation. In terms of new onset organ dysfunction, there was a significant difference between the two groups in total bilirubin at 48 h and 72 h. Based on the 60-day survival curves, there was significantly more mortality in the ScvO2 group than in the lactate kinetics group (X2 = 4.133, P = 0.042). In addition, fewer adverse events occurred in the lactate kinetics group.ConclusionsStepwise lactate kinetics-oriented hemodynamic therapy can reduce mortality in patients with sepsis-associated hyperlactatemia compared with ScvO2-oriented therapy.Trial registrationNational Institutes of Health Clinical Trials Registry, NCT02566460. Registered on 26 September 2015.

Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial

Despite the current guideline's recommendation of a timely stepwise intensification therapy, the "clinical inertia", termed as the delayed treatment intensification, commonly exists in the real world, which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy. In this clinical trial performed in 237 centers in China, 5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks. The patients who did not reach the glycated hemoglobin A1c (HbA1c) goal were then further randomized into glimepiride, gliclazide, repaglinide, or acarbose group for an additional 24-week triple therapy. A mean HbA1c reduction of 0.85% was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks. Further HbA1c reductions in the 24-week triple therapy stage were 0.65% in glimepiride group, 0.70% in gliclazide group, 0.61% in repaglinide group, and 0.45% in acarbose group. The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide, but not for acarbose, compared with glimepiride, when added to metformin/sitagliptin dual therapy. The incidences of adverse events (AEs) were 29.2% in the dual therapy stage and 30.3% in the triple therapy stage. Metformin/sitagliptin as baseline therapy, with the addition of a third oral antihyperglycemic agent, including glimepiride, gliclazide, repaglinide, or acarbose, was effective, safe and well-tolerated for achieving an HbA1c <7.0% goal in type 2 diabetic patients inadequately controlled with previous therapies. The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.

The efficacy of algorithmic antihypertensive therapy for the morning and evening home blood pressure control in real life setting

The objective. Assessment of the effectiveness stepwise algorithmic therapy for joint control of the office and home blood pressure (BP), and home morning and evening BP control in the the patients with uncomplicated hypertension (UH) in real life setting.

The effects of pure potassium channel blocker nifekalant and sodium channel blocker mexiletine on malignant ventricular tachyarrhythmias

BackgroundPatients with repetitive ventricular tachyarrhythmias — so-called electrical storm — frequently require antiarrhythmic drugs. Amiodarone is widely used for the treatment of electrical storm but is ineffective in some patients. Therefore, we investigated the efficacy of stepwise administration of nifekalant, a pure potassium channel blocker, and mexiletine for electrical storm. MethodsThis study included 44 patients with repetitive ventricular tachyarrhythmias who received stepwise therapy with nifekalant and mexiletine for electrical storm. Nifekalant was initially administered, and mexiletine was subsequently added if nifekalant failed to control ventricular tachyarrhythmias. ResultsNifekalant completely suppressed recurrences of ventricular arrhythmias in 28 patients (64%), including 6 patients in whom oral amiodarone failed to control arrhythmias. In 9 of 16 patients in whom nifekalant was partially effective but failed to suppress ventricular arrhythmias, mexiletine was added. The addition of mexiletine prevented recurrences of ventricular tachyarrhythmias in 5 of these 9 patients (56%). There was no death associated with electrical storm. In total, the stepwise treatment with nifekalant and mexiletine was effective in preventing ventricular tachyarrhythmias in 33 of 44 patients (75%). There was no difference in cycle length of the ventricular tachycardia, QRS interval, QT interval, or left ventricular ejection fraction between patients who responded to antiarrhythmic drugs and those who did not. During follow-up, 8 patients had repetitive ventricular tachyarrhythmia recurrences, and the stepwise treatment was effective in 6 of these 8 patients (75%). ConclusionsThe stepwise treatment with nifekalant and mexiletine was highly effective in the suppression of electrical storm.

SY 08-2 HYPERTENSION MANAGEMENT FOR SECONDARY PREVENTION OF STROKE

Stroke is known to frequently recur in patients with a history of cerebrovascular disease, and the control of hypertension is extremely important for the treatment of those patients. The robust relationship between the recurrent cerebrovascular disease and blood pressure control has been demonstrated in large-scale clinical studies. The antihypertensive drug therapy significantly reduces the recurrence rate of all types of cerebrovascular disease, incidences of myocardial infarction and all vascular events. Evidence suggests that any class of antihypertensive drugs including diuretics, Ca channel blockers, ARBs, and ACE inhibitors are shown to be similarly effective for the secondary prevention of stroke, except in some small study such as MOSES. Thus, most of the benefit obtained from drugs can be ascribed to a decrease in blood pressure. Then, how far should blood pressure be lowered? Target of blood pressure control has been somewhat controversial, since an excessive reduction of blood pressure might exacerbate cerebral ischemia in the area perfused by cerebral artery with a significant stenosis. In fact, some Japanese clinical study has shown that in patients with impaired perfusion demonstrated by PET-CT, the risk of recurrent stroke was high when the systolic blood pressure was There have been very few studies which have primarily investigated the optimum blood pressure level in the secondary prevention of stroke. The sub-analysis of the large clinical trial, PROGRESS, indicated that the incidences of cerebral hemorrhage and cerebral infarction were lower in patients in whom blood pressure was controlled at a lower level (a systolic blood pressure of about 120 mmHg). In the Bleeding with Antithrombotic Therapy (BAT) Study in Japan, 4,009 patients taking antithrombotic drugs for the prevention of recurrent cerebrovascular or heart disease were prospectively enrolled, and hemorrhagic events were investigated over 19 months. The results suggest that the incidence of cerebral hemorrhage is lower when the blood pressure immediately before/after onset is lower, suggesting that blood pressure should be reduced to In the Secondary Prevention of Small Subcortical Strokes (SPS3) Trial, a randomized comparative study was conducted in patients with chronic-phase lacunar infarction by dividing them into two groups: a group with a systolic blood pressure of We have been conducting a multicenter, randomized, open-label study (RESPECT study; Clinical Trials.gov Identifier: NCT01198496) since 2010, in which hypertensive patients with a history of strokes are randomly assigned to either a standard therapy group (£140/90 mmHg; if having current DM/CKD/MI, £130/80 mmHg) or a strict therapy group (BP lowering target: £120/80 mmHg). The patients were treated with stepwise multi-drug therapy using an angiotensin-receptor antagonist, diuretic, calcium channel blocker and additional other classes of drug if necessary. The recurrent stroke rates in both groups will be compared from various aspects, and whether strict BP management is useful for the prevention of recurrent strokes will be verified. The first interim analysis of this study has been recently performed. At present, in the JSH2014 Guidelines, the target of blood pressure control for patients with chronic-phase cerebral infarction is established as

Study of Insulin Requirement Modeling in Hospitalized Elderly Patients with Type 2 Diabetes at a Late Stage of Stepwise Escalation Therapy.

This study explored the relationships between exogenous insulin requirements and endogenous variables in elderly patients with type 2 diabetes (T2D). Patients with T2D 65 years of age or older were enrolled for a short hospitalization period in order to start or change their basal-bolus therapy. The following data were collected: age, sex, diabetes duration, body mass index, glycosylated hemoglobin, estimated glomerular filtration rate (eGFR), and triglyceride (TG) levels. Data from 71 elderly T2D patients (31 men/40 women; 75.7 ± 6 years of age) were analyzed by data mining techniques. The total daily dose of insulin (TDI) ranged from 0.24 U/kg to 2.5 U/kg (ratio >1:10). Three clusters of patients were identified: Cluster 1 (n = 22) consisted of older patients (age, 82.05 ± 3.6 years) (P < 0.0001) with a TDI of 0.59 ± 0.21 U/kg/day and lower TG level (1.1 ± 0.4 mmol/L) (P < 0.0001). Cluster 2 (n = 22) consisted of patients with a TDI of 0.71 ± 0.24 U/kg/day with a higher eGFR (75.3 ± 18.8 mL/min) (P < 0.001) and a shorter duration of diabetes (13.6 ± 6.4 years) (P < 0.001). Cluster 3 (n = 27) consisted of patients with a larger proportion of macroangiopathic complications (P < 0.05), having a TDI of 1.31 ± 0.54 U/kg/day, higher TG level (2.2 ± 0.7 mmol/L) (P < 0.001), and lower eGFR (46.3 ± 16 mL/min). The average basal-bolus ratio was 43%/57% with a maximum bolus requirement due to carbohydrate intake at breakfast. Insulin requirements in elderly T2D patients vary widely. Age, TG level, and eGFR appeared to be the most predictive factors of TDI. Because of the small sample size, further studies would be required to extrapolate these results.

World Gastroenterology Organisation Global Guidelines: GERD Global Perspective on Gastroesophageal Reflux Disease.

PROBIOTICS—THE CONCEPTHistory and DefinitionsA century ago, Elie Metchnikoff (a Russian scientist, Nobel laureate, and professor at the Pasteur Institute in Paris) postulated that lactic acid bacteria (LAB) offered health benefits capable of promoting longevity. He suggested that “intestinal autoint