Inappropriate use of nonsteroidal anti-inflammatory drugs and other drugs in chronic kidney disease patients without renal replacement therapy

Abstract

Objective: The main goal of chronic kidney disease (CKD) treatment is the prevention of progression of the disease and complications. Inappropriate drug use in patients with CKD is an important issue, which may cause adverse effects on patients and progression of chronic renal failure. The aim of this study is to find the rate of inappropriate drug use among CKD patients. Methods: The subjects of this study were selected from the patients with a CKD history of minimum one year, who did not receive renal replacement therapy. Patients were asked to provide a digital record of the drugs they used over the last one year. Individually, for each patient, the drugs that may be contraindicative and that require dose adjustment were identified based on glomerular filtration rate (GFR). Results: This study includes a total of 185 participants – 97 female (52.4%) and 88 male (47.6%) patients. The average age of patients was 60.50?±?14.56. It was shown that 149 patients (80.5%) were using inappropriate drugs. Seventy (47.0%) were using one, 79 (53.0%) two, 30 (20/1%) three, and 9 (6.4%) four inappropriate drugs. Of CKD patients, 44.3% were aged 65 or over; and in this age group, inappropriate drug use was more frequent compared to the population below 65 (86.6% vs. 75.7%). The drugs used inappropriately were, respectively, nonsteroidal anti-inflammatory drugs (65.8%), quinolone antibiotics (39.0%), ACE inhibitors (26.9%). Discussion: Health professionals are required to consider renal functions of all patients, mainly those aged over 65, when administering a treatment.     

Peri-operative use of nonsteroidal anti-inflammatory drugs in children: analgesic efficacy and bleeding

Nonsteroidal anti-inflammatory drugs are effective in the management of mild to moderate postoperative pain in children. They can decrease or even eliminate the need for opioid analgesics, thus reducing or eliminating opioid-induced side-effects. The increasing peri-operative use of nonsteroidal anti-inflammatory drugs in children has, however, raised concerns about complications secondary to impaired haemostasis. To examine the extent of this unwanted side-effect, this paper reviews the published literature on analgesic efficacy and bleeding following the peri-operative use of nonsteroidal anti-inflammatory drugs in children. The reviewed literature confirms that haemorrhagic events in the postoperative period occur, but results remain inconclusive regarding the association between peri-operative use of nonsteroidal anti-inflammatory drugs and disordered haemostasis. In order to maximise the benefit of nonsteroidal anti-inflammatory drugs in children, the risks must be recognised and patients, clinical indications, the individual drug, timing and route of administration must be selected carefully. Nonsteroidal anti-inflammatory drugs appear to play a valuable role in the further improvement of postoperative pain management in children.     

Influence of ageing and some lifestyle factors on male gonadal function: a study in Bulgaria

There are few systematic studies on the relationship between blood testosterone concentrations and the symptoms of androgen deficiency in ageing males. To assess the changes in sex hormone levels with age in relation with some lifestyle factors, the serum levels of total testosterone (TT), sex-hormone binding globulin (SHBG), luteinising hormone (LH) and follicle stimulating hormone (FSH) were measured in 33 men, age range 40-89 years. In addition, free testosterone (FT) and the free androgen index (FAI) were calculated. Seventeen healthy men under 40 years were involved as controls. The men over 40 years revealed significantly decreased TT, FT and FAI, and in the subgroup of men over 60 years, FSH and SHBG were significantly increased. Pearson's analysis showed that TT levels were significantly correlated with body mass index (BMI) (r = -0.464, P < 0.01) and body weight (r = -0.413, P < 0.05). SHBG levels were significantly correlated not only with age (r = +0.407, P < 0.05), but also with LH (r = +0.605, P < 0.001) and alcohol consumption (r = +0.382, P < 0.05). In conclusion, the TT, FT and FAI decreased in males over 40 years, but the alterations in hormone levels with age are more pronounced in men over 60 years. The important determinants of sex hormones are age, BMI and some lifestyle factors.     

Effects of testosterone replacement therapy on metabolic syndrome among Japanese hypogonadal men: A subanalysis of a prospective randomised controlled trial (EARTH study)

We investigated the effects of testosterone replacement therapy (TRT) on metabolic factors among hypogonadal men with a metabolic syndrome. From the study population of the EARTH study, which was a randomised controlled study in Japan, 65 hypogonadal patients with a metabolic syndrome, comprising the TRT group (n = 32) and controls (n = 33), were included in this study analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 12 months. Waist circumference, body mass index, body fat volume and blood pressure were measured in all patients at baseline and at 12 months. In addition, blood biochemical data, including total cholesterol, triglyceride (TG), HDL cholesterol, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels, were also evaluated. Changes in these categories from baseline to 12 months were compared between the TRT and control groups, with significant differences observed in waist circumference, body fat percentage, FPG, TG and HbA1c levels. No significant differences were observed in other parameters. TRT for 1 year was associated with improvements in some metabolic factors among Japanese men with hypogonadism and metabolic syndrome.     

The rationale for nonsteroidal anti-inflammatory drug therapy for inflammatory myofibroblastic tumors: a Children's Oncology Group study

Background

Inflammatory myofibroblastic tumors (IMTs) are neoplasms that are highly vascularized, have an intermediate prognosis, and are associated with infiltration, obstruction, local recurrence, and rare metastasis. Resection of large IMTs can lead to substantial morbidity and even mortality. Anecdotal experience suggests that nonsteroidal anti-inflammatory drugs may eradicate large IMTs or shrink them to a more readily resectable size and configuration. To support the hypothesis that nonsteroidal anti-inflammatory drugs are antiangiogenic for IMTs by interfering with vascular endothelial growth factor (VEGF) signaling via cyclooxygenase 2 (COX-2) inhibition, IMT specimens were immunohistochemically examined for expression of COX-2 enzyme and VEGF.

Methods

The diagnosis of IMT was confirmed in all 18 cases comprising the study. Intensity of COX-2 and VEGF staining was graded, and staining uniformity was examined. ALK-1 protein expression, found in up to two thirds of IMTs, was also determined.

Results

COX-2 and VEGF expression were identified in all tissue examined, with staining intensity varying independently. ALK-1 protein expression was identified in 33% of specimens. Its presence was not related to the intensity of COX-2 or VEGF staining.

Conclusions

Our data suggest that the mediators of angiogenesis, VEGF and COX-2, are present and may play an important role in the growth of IMTs.     

Vietnam combat exposure and recent drug use: A national study

Traumatic life experiences may have long-term adverse psychological consequences, including illicit drug use. We analyzed data from the 1985–1986 Centers for Disease Control Vietnam Experience Study to investigate this issue. Over 2,400 Vietnam veterans indicated the amount of combat to which they had been exposed, and reported on their drug use while in the Army and during the year interval prior to the interview. Combat exposure was significantly related to recent drug use, even when Army drug use and demographic factors were controlled statistically.     

Oral analgesia by non-steroidal anti-inflammatory drug zaltoprofen to manage cystoscopy-related pain: A prospective study

Objectives:   To examine the pre-emptive analgesic effect of the non-steroidal anti-inflammatory drug zaltoprofen against rigid cystoscopy-associated pain, and compare it with the effect of an anesthetic gel.
Methods:   Forty men periodically undergoing follow-up office cystoscopy were enrolled in this prospective study. The effects of lidocaine gel alone or in combination with zaltoprofen, were examined. The following parameters were assessed using an 11-point numerical rating scale: pain during injection of gel into the urethra, insertion of rigid cystoscope, and the endoscopic examination of the urinary bladder, pain at the first urination after cystoscopy, and at the first urination in the following morning at home.
Results:   Pain scores with pre-emptive zaltoprofen plus lidocaine gel were significantly lower than the ones with lidocaine gel alone at the time points of inserting rigid cystoscope into the urethra, viewing inside the urinary bladder and the first urination after cystoscopy. The efficacy of zaltoprofen was more significant in the patients with higher baseline pain score. There was no correlation between pain scores and bladder cancer grading, number of tumors, and time from surgery.
Conclusions:   Pre-emptive zaltoprofen is able to control cystoscopy-associated pain, which translates into better quality of life for patients. Thus, its use is recommended in the management of these patients.     

The efficacy of oral nonsteroidal anti-inflammatory medication (NSAID) in the treatment of plantar fasciitis: a randomized, prospective, placebo-controlled study

BACKGROUND: Plantar fasciitis frequently responds to a broad range of conservative therapies, and there is no single universally accepted way of treating this condition. Modalities commonly used include rest, ice massage, stretching of the Achilles tendon and plantar fascia, nonsteroidal anti-inflammatory medications (NSAIDs), corticosteroid injections, foot padding, taping, shoe modifications (steel shank and anterior rocker bottom), arch supports, heel cups, custom foot orthoses, night splints, ultrasound, and casting. To our knowledge, no prospective, randomized, placebo controlled double-blind study has evaluated the efficacy of oral NSAIDs in the treatment of plantar fasciitis. METHODS: Twenty-nine patients with the diagnosis of plantar fasciitis were treated with a conservative regimen that included heel-cord stretching, viscoelastic heel cups, and night splinting. They were randomly assigned to either a placebo group or an NSAID group. In the NSAID group, celecoxib was added to the treatment regimen. RESULTS: Pain and disability mean scores improved significantly over time in both groups, although there was no statistical significance between the placebo and NSAID groups at 1, 2, or 6 months. There was a trend towards improved pain relief and disability in the NSAID group, especially in the interval between the 2 and 6-month followup. Pain improved from baseline to 6 months by a factor of 5.2 and disability by 3.8 in the NSAID group compared to 3.6 and 3.5, respectively, in the placebo group. Even though at baseline the pain and disability scores were higher in the NSAID group, the final pain and disability scores were subjectively lower in the NSAID group than in the placebo group (1.43 for pain and 1.16 for disability in the NSAID group, compared to 1.86 and 1.49, respectively, in the placebo group). CONCLUSIONS: These results provide some evidence that the use of an NSAID may increase pain relief and decrease disability in patients with plantar fasciitis when used with a conservative treatment regimen.     

Primary gonadal failure in men selectively amplifies the mass of follicle stimulating hormone (FSH) secreted per burst and increases the disorderliness of FSH release patterns: reversibility with testosterone replacement

The neuroendocrine mechanisms by which primary gonadal failure in men increases mean serum FSH concentrations (castration-like response) are not known. To investigate the testosterone-dependent mechanisms of the FSH castration response: (i) blood was sampled at 10-min intervals for 24 h for later FSH assay in seven normal middle-aged men and in six patients with primary testicular failure, during testosterone withdrawal and after 6 weeks of parenteral testosterone replacement; (ii) using a specific two-site IRMA, serum FSH concentrations were measured, since this assay correlates well with an in-vitro Sertoli cell bioassay; (iii) multiparameter deconvolution analysis was then applied to estimate the frequency, amplitude, duration, and mass of underlying FSH secretory bursts, and the half-life of endogenous FSH, and (iv) approximate entropy was calculated to quantify the relative orderliness of FSH release over 24 h. Mean (+/- SEM) 24-h serum FSH concentrations were 3.9 +/- 0.8 IU/L in control subjects and 39 +/- 10 IU/L in unreplaced hypogonadal patients (p = 0.034). Deconvolution analysis revealed similar estimated mean FSH half-lives of 346 +/- 40 min (control) and 321 +/- 47 min (untreated patients), and indistinguishable FSH secretory burst frequencies, namely, 20 +/- 0.95 (normal) and 21 +/- 1.3 (patients) pulses per 24 h. In contrast, the daily production rate of FSH was markedly increased in testosterone-withdrawn hypogonadal men at 117 +/- 25 vs. 9.3 +/- 1.8 IU/L/day (control) (p < 0.01). This was due to a 10-fold higher calculated maximal rate (amplitude) of FSH secretion achieved within each FSH release episode (normal 0.078 +/- 0.02 vs. gonadal failure 0.74 +/- 0.087 IU/L/min, p < 0.01), yielding a 10-fold increase in the mass of FSH secreted per burst (control 0.53 +/- 0.06 vs. patients 5.3 +/- 0.81 IU/L, p < 0.01). In contrast, the mean half-duration of FSH secretory bursts was unaltered in unreplaced hypogonadal men at 8.2 +/- 2.2 min (control) vs. 7.0 +/- 1.0 min (patients). Approximate entropy (ApEn), a scale- and model-independent statistic designed to quantify the orderliness or regularity of hormone release, revealed greater irregularity of serum FSH concentrations in the hypoandrogenic state: ApEn = 1.8 +/- 0.025 (testosterone-withdrawn) vs. 1.6 +/- 0.037 (control) (p < 0.05). Parenteral testosterone replacement for 6 weeks significantly decreased mean serum FSH concentrations by reducing the daily FSH secretion rate and FSH secretory burst amplitude and mass, and concomitantly restored the orderliness of FSH release patterns. Testosterone treatment did not change FSH secretory burst half-duration, number, interburst interval, or half-life. It is concluded that primary gonadal failure in men evokes FSH hypersecretion which is marked by more disorderly FSH release patterns and a selectively amplified mass of FSH secreted per burst. These hypergonadotrophic mechanisms are, to a significant extent, testosterone-suppressible.     

Efficacy of testosterone replacement therapy on pain in hypogonadal men with chronic pain syndrome: A subanalysis of a prospective randomised controlled study in Japan (EARTH study)

The present study investigated the efficacy of 6 months of testosterone replacement therapy (TRT) on chronic pain syndrome in late-onset hypogonadal (LOH) men. Sixty hypogonadal patients with chronic pain syndrome (31 patients in TRT group and 29 controls) were extracted from a previous randomised controlled study in Japan. Chronic pain was evaluated based on bodily pain (BP) subscale of Short-form (36) Health Survey (SF-36), and patients with a score of 50.0 or less were defined as suffering from chronic pain. SF-36 scores, Aging Male Symptoms (AMS) scale, international prostatic symptoms score (IPSS) and prostate-specific antigen (PSA) levels at baseline and a 6-month visit for the two groups were collected and compared. There were no statistically significant differences in baseline backgrounds between the two groups. Six-month TRT could contribute to significant improvements in BP, mental health of SF-36 and sleep disturbance (AMS question 4). Though the PSA level in the TRT group also significantly elevated at 6 months, the increase was not clinically significant. No significant improvements were evident in any characteristics in the controls. In conclusion, 6-month TRT can improve pain and some aspects of quality of life in LOH men with chronic pain.     

Effects of a short course of oral phosphate treatment on serum parathyroid hormone (1–84) and biochemical markers of bone turnover: A dose-response study

Summary To investigate the possible use of oral phosphate as an activator of bone remodeling in coherence treatment of osteoporosis, 82 postmenopausal females, aged 50–75 years, were randomized to treatment with oral phosphate (750, 1500, or 2550 mg/day) or placebo for 7 days and followed for 4 months thereafter. All patients had sustained at least one previous fracture of the distal forearm and had a bone mineral content of the contralateral forearm or bone mineral density of the lumbar spine lower than normal mean for age. Urinary phosphate/creatinine ratio increased in a dose-dependent fashion during treatment (P<0.001), whereas no significant changes were seen in serum phosphate or serum calcium. Serum parathyroid hormone (PTH) rose significantly (P<0.05) during treatment to a maximum of 36 and 33% in the groups receiving 1500 and 2250 mg/day, respectively, whereas serum 1,25-dihydroxycholecalciferol remained unchanged. In the group receiving 1500 mg/day, mean serum osteocalcin was increased in the period from day 1 to day 28 (P<0.05), but no significant changes were observed in urinary hydroxyproline/creatinine ratio, or serum bone alkaline phosphatase. We conclude that a short course of oral phosphate treatment increases serum PTH considerably. Furthermore, 1500 mg/day but not 2250 mg/day increases serum osteocalcin. No clear biochemical evidence, however, of increased activation of bone remodeling could be demonstrated in either group.     

A phase II study of mifepristone (RU-486) in castration-resistant prostate cancer, with a correlative assessment of androgen-related hormones

OBJECTIVE

To evaluate mifepristone (RU‐486) in patients with castration‐resistant prostate cancer (CRPC), with a correlative assessment of serum androgens and androgen metabolites

PATIENTS AND METHODS

The androgen receptor (AR) is critical in the development and progression of prostate cancer, but available antiandrogens incompletely abrogate AR signalling. Mifepristone is a potent AR antagonist that functions by competing with androgen, preventing AR coactivator binding and by enhancing binding of AR corepressors. Patients with CRPC were treated with mifepristone 200 mg/day oral until disease progression. Testosterone, dihydrotestosterone (DHT), androstenedione, dihydroepiandrosterone sulphate and the testosterone metabolite 3α‐diol G, were measured at baseline and during therapy.

RESULTS

Nineteen patients were enrolled between April and August 2005; they were treated for a median (range) of 85 (31–338) days. The median prostate‐specific antigen (PSA) level at enrolment was 22.0 (3.0–937.2) ng/mL. No patient had a PSA response (>50% reduction in PSA). Six patients had stable disease for a median of 5.5 months. After 1 month, adrenal androgens were increased and testosterone and DHT increased by 91% and 80%, respectively, compared to baseline.

CONCLUSION

Mifepristone had limited activity in patients with CRPC, and stimulated a marked increase in adrenal androgens, testosterone and DHT. We hypothesise that inhibition of glucocorticoid receptor by mifepristone resulted in an increase in adrenocorticotropic hormone and subsequent increase in adrenal androgens, and that their conversion by tumour cells to testosterone and DHT probably limited the efficacy of mifepristone. These data emphasize the continued importance of alternative androgen sources in AR signalling in CRPC.     

Management of the non-descended testis: doubtful value of luteinizing-hormone-releasing-hormone (LHRH). A double-blind, placebo-controlled multicentre study

In a double-blind, placebo-controlled multicentre study, the effect of luteinizing-hormone-releasing-hormone (LHRH) in 141 boys was analysed after 4-week treatment period with 0.4 mg LHRH nasal spray or placebo nasal spray three times daily. Data from 123 boys was analysed, with 62 boys in the treatment group and 61 in the placebo group. Full response i.e. the testis at the bottom of the scrotum on both sides in boys with bilaterally undescended testes, was found in six patients, one of them in the placebo group [Therapeutic gain of LHRH with 95% CI: 8.1% (0.1-16.6%, P = 0.12)]. Only in these boys could surgery be avoided. Considering the number of testes (and not the number of boys) a significant effect was found on at least one testis in 25% of boys with bilaterally undescended testes [Therapeutic gain with 95% CI: 24.0% (13.2-34.8%, P = 0.001)]. In unilateral undescended testes, the LHRH treatment showed no effect (P = 1.00). The inclusion of retractile testes did not affect our results. In our opinion LHRH has a limited place in treatment of the non-descended testis.     

Hand therapist use of patient report outcome (PRO) in practice: A survey study

PurposeThe purpose of this survey was to gain greater insight into hand therapists' use of Patient Report Outcome (PRO) measures.MethodsAn 11-question survey that evaluated therapists' perceptions, preferences, and patterns of use of patient report outcome measures was sent to members of ASHT.ResultsA total of 633 ASHT members participated in the survey study. A large majority of participants (92%) responded affirmatively to using a PRO measure in practice. The DASH was reported as the most frequently used measure (90%). The majority of therapists (84%) discuss the results of the outcome measurement score with their patients. Of the participants who use more than one outcome measure, 44% report that this allows them to better establish their patient's functional and physical limitations.ConclusionThe findings in this study suggest that a large percentage of hand therapists are currently including a PRO measure in their hand therapy practice.     

Driver sleepiness and risk of motor vehicle crash injuries: A population-based case control study in Fiji (TRIP 12)

Introduction

Published studies investigating the role of driver sleepiness in road crashes in low and middle-income countries have largely focused on heavy vehicles. We investigated the contribution of driver sleepiness to four-wheel motor vehicle crashes in Fiji, a middle-income Pacific Island country.

Method

The population-based case control study included 131 motor vehicles involved in crashes where at least one person died or was hospitalised (cases) and 752 motor vehicles identified in roadside surveys (controls). An interviewer-administered questionnaire completed by drivers or proxies collected information on potential risks for crashes including sleepiness while driving, and factors that may influence the quantity or quality of sleep.

Results

Following adjustment for confounders, there was an almost six-fold increase in the odds of injury-involved crashes for vehicles driven by people who were not fully alert or sleepy (OR 5.7, 95%CI: 2.7, 12.3), or those who reported less than 6 h of sleep during the previous 24 h (OR 5.9, 95%CI: 1.7, 20.9). The population attributable risk for crashes associated with driving while not fully alert or sleepy was 34%, and driving after less than 6 h sleep in the previous 24 h was 9%. Driving by people reporting symptoms suggestive of obstructive sleep apnoea was not significantly associated with crash risk.

Conclusion

Driver sleepiness is an important contributor to injury-involved four-wheel motor vehicle crashes in Fiji, highlighting the need for evidence-based strategies to address this poorly characterised risk factor for car crashes in less resourced settings.     

Serum levels of bone GLA protein (osteocalcin,BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegly: Effects of long-term octreotide treatment

Summary We measured serum concentrations of bone Glaprotein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150–450 g/day for 6–33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2±4.2 g/liter versus 8.0±3.3 g/liter, P<0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r=0.67, P<0.001). Also IGF-I concentrations were positively correlated with BGP (r=0.66, P<0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146±46 g/liter versus 127±44 g/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.