Medicine by Alexandros G. Sfakianakis: Therapeutics

Δευτέρα 22 Ιουλίου 2019

Therapeutics

Sexual Functioning in Hyperprolactinemic Patients Treated With Cabergoline or Bromocriptine

Background: Elevated prolactin levels were found to be associated with impaired sexuality. Study Question: The aim of the study was to compare the impact of bromocriptine and cabergoline on sexual functioning in both genders. Study Design: The study enrolled 39 young women and 18 young men receiving bromocriptine treatment. In 19 women and 8 men, because of poor tolerance, bromocriptine was replaced with cabergoline, whereas the remaining ones continued bromocriptine treatment. Measures and Outcomes: Apart from measuring serum levels of prolactin and insulin sensitivity, at the beginning of the study and 16 weeks later, all included patients completed questionnaires evaluating female or male sexual functioning (Female Sexual Function Index; International Index of Erectile Function-15). Results: Irrespective of the gender, posttreatment prolactin levels were lower in cabergoline-treated patients than in bromocriptine-treated patients. Baseline sexual functioning did not differ between patients well and poorly tolerating bromocriptine treatment. Neither in men nor in women receiving bromocriptine, posttreatment sexual functioning differed from baseline one. In both genders, cabergoline improved sexual desire. Moreover, in men, the drug improved erectile and orgasmic function, whereas in women, it improved sexual arousal. All these effects correlated with the impact of this drug on prolactin levels and on insulin sensitivity. Conclusions: Cabergoline is superior to bromocriptine in affecting male and female sexual functioning and should be preferred in hyperprolactinemic men and women with sexual dysfunction.

Effect of Treating Vitamin D Deficiency in Uncontrolled Type 2 Diabetes: A Randomized, Placebo-Controlled Study

Background: Literature increasingly supports the inverse relationship of vitamin D (VitD) level and type 2 diabetes (T2DM). Proposed protective mechanisms of VitD include its anti-inflammatory effects, increased insulin secretion via pancreatic β-cell stimulation, and downregulation of parathyroid hormone levels. Interventional studies show mixed results of VitD therapy in prediabetic patients with VitD deficiency or diabetic patients with normal VitD levels. Study Question: Does high-dose VitD replacement improve glycemic control and microalbuminuria (MAU) in uncontrolled T2DM and concurrent VitD deficiency? Study Design: This placebo-controlled, double-blinded study randomized 30 subjects aged 30–65 years with an elevated HbA1c level of 7.5%–10% and a low total 25-hydroxyvitamin-D value of <20 ng/mL to either placebo (n = 16) or ergocalciferol 50,000 IU (n = 14) once weekly for 8 weeks then once monthly for 4 months. Measures and Outcomes: Primary outcome was difference in HbA1c from baseline to month 6 between the VitD-intervention group and the placebo-controlled group. Secondary end points were differences in total 25-hydroxyvitamin-D and MAU. Paired t tests and linear mixed-effects models were used for statistical analysis. Results: No significant differences were seen in HbA1c or MAU between baseline versus postintervention visits within the placebo group (HbA1c: 8.4% ± 0.2 vs. 8.1% ± 0.3, P = 0.088; MAU: 94.1 mg/g ± 43.9 vs. 45.9 mg/g ± 20.2, P = 0.152) and the intervention group (HbA1c: 8.8% ± 0.3 vs. 8.7% ± 0.4, P = 0.692; MAU: 167.8 mg/g ± 70.1 vs. 108.5 mg/g ± 39.9, P = 0.356). The difference between placebo-slope and intervention-slope was nonsignificant for MAU (β = −0.1 mg/g ± 0.4, P = 0.835) but was significant for total 25-hydroxyvitamin-D (β = 11.7 ng/mL ± 2.5, P ≤ 0.001). Greater HbA1c reduction occurred unexpectedly in the placebo group ( JOURNAL/ajthe/04.02/00045391-201908000-00002/math_2MM1/v/2019-07-21T181442Z/r/image-tiff = −0.4% ± 0.2) than in the intervention group ( JOURNAL/ajthe/04.02/00045391-201908000-00002/math_2MM2/v/2019-07-21T181442Z/r/image-tiff = −0.2% ± 0.4), although the difference in slopes was not significant (β = 0.2% ± 0.4, P = 0.640). Conclusions: Our proof-of-concept study found no benefit of high-dose VitD therapy in glycemic control and MAU in uncontrolled T2DM and VitD deficiency. Post hoc analyses raise concerns for high-dose VitD therapy to delay glycemic improvement. Large-scale interventional trials are much needed in this patient population to substantiate our findings and elucidate VitD's mechanisms on glucose metabolism.

Therapeutic Outcome of Achalasia Based on High-Resolution Manometry: A Korean Multicenter Study

Background: Because achalasia subtype is associated with therapeutic response, it is possible that regional differences in subtype distribution could lead to differences in therapeutic outcomes. Study Question: We aimed to evaluate and compare high-resolution manometry (HRM) profiles among the different subtypes of achalasia and to elucidate predictive factors associated with treatment outcomes. Study Design: Patients who were diagnosed with achalasia using HRM at 4 Korean university hospitals were retrospectively identified and analyzed. Sixty-four patients with untreated achalasia were divided into 3 subtypes using the Chicago classification system. Measures and Outcomes: Clinical characteristics, manometric features, and treatment outcomes were compared. Results: Among 64 patients diagnosed with achalasia, 31 patients were classified as type I, 27 as type II, and 6 as type III. Regarding HRM parameters, there were statistically significant differences in basal lower esophageal sphincter pressure, 4-second-integrated relaxation pressure, residual upper esophageal sphincter pressure, body amplitude, and maximal intrabolus pressure between subtypes. Regarding therapeutic outcome, type II patients (overall success rate of 80.0%) were more likely to respond than type I (55.2%) or type III (33.2%) patients. Multivariate analysis demonstrated that achalasia subtype (type I vs. III, P = 0.072; type II vs. III, P = 0.005), therapeutic modality (dilation vs. pharmacologic, P = 0.013; laparoscopic Heller's myotomy vs. pharmacologic, P = 0.006), and HRM-measured esophageal length (<27.5 vs. ≥27.5 cm, P = 0.014) are independent predictive factors for therapeutic failure. Conclusions: Patients with type II achalasia had better treatment outcomes than patients with other achalasia subtypes. Achalasia subtype, therapeutic modality, and esophageal length are independent predictive factors of therapeutic outcome.

Enhancing HIV Pre-exposure Prophylaxis Practices via an Educational Intervention

Background: Pre-exposure prophylaxis (PrEP) for HIV involves using antiretroviral drugs to prevent individuals at high risk from acquiring HIV infection. Most practicing primary care providers believe PrEP to be safe and effective, but less than half have prescribed or referred for PrEP. Attitudes and prescribing patterns among house officers have not been well described previously. Study Question: Can an educational intervention enhance HIV PrEP practices among internal medicine house officers? Study Design: This study relied on a pretest/posttest design. All categorical trainees at a medium-sized internal medicine program were offered a baseline survey to assess their knowledge on PrEP. This was followed by a PrEP-focused educational intervention and a postintervention survey. Measures and Outcomes: Likert scales captured perceptions regarding safety, effectiveness, barriers, factors that would promote PrEP use, potential side effects, impact on risk-taking behavior, and provider comfort level in assessing behavioral risks and in PrEP prescribing. Data were analyzed using descriptive statistics, Wilcoxon signed rank test, and the Kruskal–Wallis test. Significance was accepted for P < 0.05. Results: Forty-eight (100%) trainees participated in the educational session, 45 (94%) in a preintervention survey, and 36 (75%) in a postintervention survey. Before PrEP training, 22% of respondents were unaware of PrEP, 78% believed PrEP was effective, 66% believed PrEP was safe, 62% had fair or poor awareness of side effects; 18% of residents had referred for or prescribed PrEP, and 31% believed they were likely to prescribe PrEP in the next 6 months. After the intervention, 94% of trainees believed PrEP was effective (P < 0.001), 92% believed PrEP was safe (P < 0.001), and two-thirds believed they were likely to prescribe PrEP in the next 6 months. Conclusions: Brief, focused training on HIV prevention promotes awareness, acceptance, and likelihood of prescribing PrEP by internal medicine trainees.

Prevention of Recurrent Ventricular Tachycardia in Patients With Implantable Cardioverter Defibrillators—A Network Meta-analysis

Background: The optimal management for the prevention of recurrent ventricular tachycardia in patients with implantable cardioverter-defibrillators (ICDs) offers a challenge with no set guidelines regarding which therapy offers a best safety and efficacy profile. Study Question: Which therapeutic strategy, among antiarrhythmic drugs and catheter ablation (CA), offers the most effective and safe approach in patients with ICDs? Data Sources: Randomized controlled trials (RCTs) comparing the efficacy and safety of antiarrhythmic drugs or CA against a placebo group. RCTs were identified from a comprehensive search in PubMed, Embase, and Cochrane library. Study Design: Our outcomes of interest were reductions in appropriate ICD shocks, inappropriate ICD shocks, and overall mortality. We used the event rates in both groups, and then using a frequentist approach employing a graph theory methodology, we constructed a network meta-analysis model. Results: Fourteen RCTs with 3815 participants and 6 different interventions treatments were included in our network meta-analysis. The most effective treatment for the prevention of recurrent ventricular tachycardia after ICD is amiodarone followed by CA. Amiodarone is most effective in the reduction of appropriate and inappropriate ICD shocks with an odds ratio (OR) of 0.29 [95% confidence interval (CI), 0.11–0.74] and 0.15 (95% CI, 0.04–0.60), respectively. CA was effective in the reduction of appropriate ICD shocks (OR, 0.41; 95% CI, 0.20–0.87), whereas sotalol was effective in the reduction of inappropriate ICD shocks (OR, 0.46; 95% CI, 0.22–0.95). There was no significant reduction in the overall mortality from any therapy. There was a trend of increased mortality associated with amiodarone therapy (OR, 2.40; 95% CI, 0.92–6.26). Conclusions: Amiodarone remains the most efficacious therapy for the reduction of appropriate and inappropriate shocks in patients with ICD. No therapy resulted in mortality reduction, but amiodarone showed a trend toward increased mortality.

Fingolimod-Associated Intracerebral Lymphoproliferative Disorder

Most epidemiological studies indicate that incidence of cancer in multiple sclerosis patients is lower than general population. However these studies were performed prior to the emergence of disease-modifying therapies (DMTs). The incidence of cancer may be influenced by newer generation DMTs which are immunomodulatory or immunosuppressant. We describe an atypical case of intracerebral plasmacytic lymphoproliferative disorder in a 47 years old patient on fingolimod. As worldwide usage of oral and infusion DMTs increases, heightened clinical suspicion and early recognition of these serious adverse events remain crucial.

Intravenous Immunoglobulin and Methylprednisolone for Clozapine-Associated Perimyocarditis
Clinical Features: Cardiotoxicity is a rare but serious side effect of clozapine. We present a case of a psychiatric patient on chronic clozapine 75 mg daily, who presented with congestive heart failure secondary to the cardiotoxic effects of the psychiatric medication. Therapeutic Challenge: Conventional heart failure treatment failed to improve symptoms. Solution: A course of 40 mg of intravenous immunoglobulin and 125 mg of steroids was implemented, after which the patient made a full recovery. We hope to raise awareness of concurrent clozapine-induced pericarditis and myocarditis and propose a role of intravenous immunoglobulin and steroids in the treatment of drug-induced cardiomyopathy.

Intravenous Lidocaine for Intractable Renal Colic Unresponsive to Standard Therapy
Clinical Features: Renal colic is defined as a flank pain radiating to the groin caused by kidney stones in the ureter (urolithiasis). Renal colic is a frequent cause of Emergency Department visits. Most renal colic cases present as acute distress and severe back and/or abdominal pain that require prompt treatment with analgesics. Therapeutic Challenge: Nonsteroidal anti-inflammatory drugs and opioids are traditionally used for renal colic in the Emergency Department. This trend of practice is based on clinical experience and expert opinion. Consensus guidelines that provide evidence-based approach for the management of renal colic are limited. One consensus guideline from Europe provides a systematic approach for the management of pain with the use of nonsteroidal anti-inflammatory drugss and opioids. However, no guidance is provided on how to manage patients who do not respond to these agents. Solution: Intravenous lidocaine 120 mg in 100 mL normal saline was infused over 10 minutes for pain management for intractable renal colic unresponsive to standard therapy. Three minutes after initiation of lidocaine infusion, the patient reported numeric pain rating scale 1/10. At 5 minutes, the reported numeric pain rating scale was 0/10 and remained for 60 minutes after initiation of lidocaine infusion. No adverse events were reported during or after the infusion, and no subsequent analgesia was required.

Intravenous Fluid Therapy in Hospitalized Patients