Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis.

Background: Testosterone is the standard treatment for male hypogonadism, but there is uncertainty about its cardiovascular safety due to inconsistent findings. We aimed to provide the most extensive individual participant dataset (IPD) of testosterone trials available, to analyse subtypes of all cardiovascular events observed during treatment, and to investigate the effect of incorporating data from trials that did not provide IPD. Methods: We did a systematic review and meta-analysis of randomised controlled trials including IPD. We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Epub Ahead of Print, Embase, Science Citation Index, the Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and Database of Abstracts of Review of Effects for literature from 1992 onwards (date of search, Aug 27, 2018). The following inclusion criteria were applied: (1) men aged 18 years and older with a screening testosterone concentration of 12 nmol/L (350 ng/dL) or less; (2) the intervention of interest was treatment with any testosterone formulation, dose frequency, and route of administration, for a minimum duration of 3 months; (3) a comparator of placebo treatment; and (4) studies assessing the pre-specified primary or secondary outcomes of interest. Details of study design, interventions, participants, and outcome measures were extracted from published articles and anonymised IPD was requested from investigators of all identified trials. Primary outcomes were mortality, cardiovascular, and cerebrovascular events at any time during follow-up. The risk of bias was assessed using the Cochrane Risk of Bias tool. We did a one-stage meta-analysis using IPD, and a two-stage meta-analysis integrating IPD with data from studies not providing IPD. The study is registered with PROSPERO, CRD42018111005. Findings: 9871 citations were identified through database searches and after exclusion of duplicates and of irrelevant citations, 225 study reports were retrieved for full-text screening. 116 studies were subsequently excluded for not meeting the inclusion criteria in terms of study design and characteristics of intervention, and 35 primary studies (5601 participants, mean age 65 years, [SD 11]) reported in 109 peer-reviewed publications were deemed suitable for inclusion. Of these, 17 studies (49%) provided IPD (3431 participants, mean duration 9·5 months) from nine different countries while 18 did not provide IPD data. Risk of bias was judged to be low in most IPD studies (71%). Fewer deaths occurred with testosterone treatment (six [0·4%] of 1621) than placebo (12 [0·8%] of 1537) without significant differences between groups (odds ratio [OR] 0·46 [95% CI 0·17-1·24]; p=0·13). Cardiovascular risk was similar during testosterone treatment (120 [7·5%] of 1601 events) and placebo treatment (110 [7·2%] of 1519 events; OR 1·07 [95% CI 0·81-1·42]; p=0·62). Frequently occurring cardiovascular events included arrhythmia (52 of 166 vs 47 of 176), coronary heart disease (33 of 166 vs 33 of 176), heart failure (22 of 166 vs 28 of 176), and myocardial infarction (10 of 166 vs 16 of 176). Overall, patient age (interaction 0·97 [99% CI 0·92-1·03]; p=0·17), baseline testosterone (interaction 0·97 [0·82-1·15]; p=0·69), smoking status (interaction 1·68 [0·41-6·88]; p=0.35), or diabetes status (interaction 2·08 [0·89-4·82; p=0·025) were not associated with cardiovascular risk. Interpretation: We found no evidence that testosterone increased short-term to medium-term cardiovascular risks in men with hypogonadism, but there is a paucity of data evaluating its long-term safety. Long-term data are needed to fully evaluate the safety of testosterone. Funding: National Institute for Health Research Health Technology Assessment Programme.

Testosterone deficiency syndrome among males with type 2 diabetes mellitus in East Malaysia.

Type 2 diabetes mellitus (T2DM) may be independently associated with testosterone deficiency syndrome (TDS). Both conditions are linked with reduced quality of life and cardiovascular comorbidities. The magnitude of TDS among T2DM men and its predictors has still not been well established in Malaysia. This study aimed to determine the prevalence of TDS and its predictors among men with T2DM attending a government health clinic in Kuching, Sarawak. TDS severity and level of serum total testosterone were also explored. A cross-sectional study was conducted involving 360 respondents. Aging Males Symptoms Scale (AMS) score > 26 and serum total testosterone ≤ 12 nmol/L were used to diagnose TDS. The prevalence of TDS in current study was 19.7%. Multivariate analysis showed that determinants for TDS included age (Adjusted OR 1.061: 95% CI 1.020; 1.103), Iban ethnicity (Adjusted OR 2.469: 95% CI 1.154; 5.283) and a waist circumference equal or greater than 90 cm (Adjusted OR 3.655: 95% CI 1.472; 9.081). However, there was no significant association between TDS and the level of serum total testosterone (p = 0.581). We concluded that the prevalence of TDS in this study was relatively low. The severity of this condition may not be influenced by testosterone level. Physicians might consider a diagnosis of TDS if elder diabetic men with abdominal obesity present to primary care clinics with clinical features of hypogonadism. Health care providers also might consider lowering their threshold to screen for TDS among Iban men with T2DM.

The Impact of Dry Needling on Patients with Neck Pain in a Tertiary Hospital

Neck pain presents as a symptom of dull pain or discomfort mainly along the trapezius muscle. Dry needling is an invasive procedure which uses acupuncture needle directed at myofascial trigger points. The aim of the study was to evaluate the effectiveness of dry needling in managing patients with neck pain. A pre-test-post-test interventional study design was used. Patient education package was provided to 32 respondents who fulfilled the inclusion criteria. A 13-item Pain Catastrophizing Scale (PCS) questionnaire was used to assess Rumination, Magnification and Helplessness. Subjective pain intensity was measured by Visual Analogue Scale (VAS). These questionnaires were given before and after the dry needling intervention. The findings reported that respondents scored high in pre-test total PCS score (27.41±13.652). Post-test result revealed a significant improvement in total PCS score (23.06±13.938) (p = 0.000). Post-test VAS score (4.78±1.237) was also significantly better than pre-test (6.47±1.414) (p = 0.000). There was no significant difference in pre-test PCS in terms of marital status (p > 0.05) whereas there was significant difference between marital status and rumination in post-test (Z = -2.303, p = 0.021). There was significant difference between pre-test magnification in terms of respondents’ occupation (p = 0.008) and race (p = 0.035) but no significant difference in post-test. Respondents’ age group showed no significant differences between pre-test and post-test PCS and VAS (p > 0.05). In conclusion, patients who received dry needling showed improvement in pain intensity and catastrophizing towards neck pain.

Diabetes Mellitus and Diet: Few Important Facts to Ponder / Jurnal Sains Kesihatan Malaysia

Diabetes mellitus (DM) is a metabolic disease which is characterized by hyperglycemia. There is either disturbance in insulin secretion or defective insulin action or even a combination of both. Usually, there are few confounding factors like genetic, obesity, sedentary life style, atherosclerosis, and even faulty dietary habits which lead or aggravate DM. Usually, the individual does not care and often the complications resulting from hyperglycaemia are fatal. Complications in DM involve the cardiovascular, musculoskeletal, endocrine, renal and neurological systems in the body. Treatment of diabetic complications is not only costly but it is also a burden on the affected families. The present review discusses the challenges faced in DM with special concern on diet and food habits. Knowledge of proper food consumption may also help an individual combat complication in DM and reduce the mortality and morbidity.

Asian Men’s Health: Gender Disparity and Life Expectancy

The aim of this review was to analyze the gender disparities found as well as the life expectancies in Asia. An analysis of the data on gender disparities as well as life expectancies of the different Asian countries was done based on the World Health Organization (WHO) Global Health Observatory Data Repository as well as the regional government databases. Middle Eastern countries have the highest male to female population ratio. The results show that in terms of population pyramid, Asia is moving towards a more geriatric population. Qatar has the highest life expectancy for men and is the only country in Asia where men live longer than women (difference of 2 years). In general, women in Asia live longer than men. High income countries like Hong Kong, Japan and Singapore have higher life expectancies as compared to those on the lower income nations. The life expectancy of Asian men still lags women. Men’s health care needs to be addressed urgently. The disparity in income-status reflecting the lifespan of men is an impetus for us to narrow the gap of health in Asian countries.

Human adipose tissue derived stem cells as a source of smooth muscle cells in the regeneration of muscular layer of urinary bladder wall.

BACKGROUND: Adipose tissue provides an abundant source of multipotent cells, which represent a source of cell-based regeneration strategies for urinary bladder smooth muscle repair. Our objective was to confirm that adipose-derived stem cells (ADSCs) can be differentiated into smooth muscle cells. METHODS: In this study, adipose tissue samples were digested with 0.075% collagenase, and the resulting ADSCs were cultured and expanded in vitro. ADSCs at passage two were differentiated by incubation in smooth muscle inductive media (SMIM) consisting of MCDB I31 medium, 1% FBS, and 100 U/mL heparin for three and six weeks. ADSCs in non-inductive media were used as controls. Characterisation was performed by cell morphology and gene and protein expression. RESULT: The differentiated cells became elongated and spindle shaped, and towards the end of six weeks, sporadic cell aggregation appeared that is typical of smooth muscle cell culture. Smooth muscle markers (i.e. alpha smooth muscle actin (ASMA), calponin, and myosin heavy chain (MHC)) were used to study gene expression. Expression of these genes was detected by PCR after three and six weeks of differentiation. At the protein expression level, ASMA, MHC, and smoothelin were expressed after six weeks of differentiation. However, only ASMA and smoothelin were expressed after three weeks of differentiation. CONCLUSION: Adipose tissue provides a possible source of smooth muscle precursor cells that possess the potential capability of smooth muscle differentiation. This represents a promising alternative for urinary bladder smooth muscle repair.

Stratifying patients with haematuria into high or low risk groups for bladder cancer: a novel clinical scoring system.

Haematuria is a common presentation of bladder cancer and requires a full urologic evaluation. This study aimed to develop a scoring system capable of stratifying patients with haematuria into high or low risk groups for having bladder cancer to help clinicians decide which patients need more urgent assessment. This cross- sectional study included all adult patients referred for haematuria and subsequently undergoing full urological evaluation in the years 2001 to 2011. Risk factors with strong association with bladder cancer in the study population were used to design the scoring system. Accuracy was determined by the area under the receiver operating characteristic (ROC) curve. A total of 325 patients with haematuria were included, out of which 70 (21.5%) were diagnosed to have bladder cancer. Significant risk factors associated with bladder cancer were male gender, a history of cigarette smoking and the presence of gross haematuria. A scoring system using 4 clinical parameters as variables was created. The scores ranged between 6 to 14, and a score of 10 and above indicated high risk for having bladder cancer. It was found to have good accuracy with an area under the ROC curve of 80.4%, while the sensitivity and specificity were 90.0% and 55.7%, respectively. The scoring system designed in this study has the potential to help clinicians stratify patients who present with haematuria into high or low risk for having bladder cancer. This will enable high-risk patients to undergo urologic assessment earlier.

Human Adipose Tissue Derived Stem Cells as a Source of Smooth Muscle Cells in the Regeneration of Muscular Layer of Urinary Bladder Wall

Background: Adipose tissue provides an abundant source of multipotent cells, which represent a source of cell-based regeneration strategies for urinary bladder smooth muscle repair. Our objective was to confirm that adipose-derived stem cells (ADSCs) can be differentiated into smooth muscle cells. Methods: In this study, adipose tissue samples were digested with 0.075% collagenase, and the resulting ADSCs were cultured and expanded in vitro. ADSCs at passage two were differentiated by incubation in smooth muscle inductive media (SMIM) consisting of MCDB I31 medium, 1% FBS, and 100 U/mL heparin for three and six weeks. ADSCs in non-inductive media were used as controls. Characterisation was performed by cell morphology and gene and protein expression. Result: The differentiated cells became elongated and spindle shaped, and towards the end of six weeks, sporadic cell aggregation appeared that is typical of smooth muscle cell culture. Smooth muscle markers (i.e. alpha smooth muscle actin (ASMA), calponin, and myosin heavy chain (MHC)) were used to study gene expression. Expression of these genes was detected by PCR after three and six weeks of differentiation. At the protein expression level, ASMA, MHC, and smoothelin were expressed after six weeks of differentiation. However, only ASMA and smoothelin were expressed after three weeks of differentiation. Conclusion: Adipose tissue provides a possible source of smooth muscle precursor cells that possess the potential capability of smooth muscle differentiation. This represents a promising alternative for urinary bladder smooth muscle repair.

Iatrogenic Ureter Injuries: Eleven Years Experience in A Tertiary Hospital

Iatrogenic ureteric injuries are rare complications of abdomino-pelvic surgery but associated with high morbidity from infection and possible loss of renal function. A successful repair is related to the timing of diagnosis, site of injury and method of repair. This study was a retrospective review of outcomes of iatrogenic ureteric injury and factors contributing to successful operative repair. Twenty consecutive cases referred to the Urology Unit of the UKM Medical Center during an 11-year period from 1998 to 2009 were reviewed. Thirteen patients were diagnosed intraoperatively and underwent immediate repair. Seven patients had delayed diagnosis but also underwent immediate repair. In our series, there was no significant difference in outcome between injuries diagnosed intraoperatively versus injuries with delayed diagnosis. There was significant difference in the outcomes between methods of ureteric repair where ureter reimplantation via psoas hitch or Boari flap yielded better results than primary end-to-end anastomosis Three patients suffered loss of renal function from unsuccessful ureter repair. We conclude that all iatrogenic ureteric injury should be repaired immediately in the absence of overt sepsis. Ureter reimplantation using a Boari flap or psoas hitch is preferred to the end-to-end anastomosis especially when there is delayed diagnosis

Prevalence and Awareness of Lower Urinary Tract Symptoms among Males in the Outpatient Clinics of Universiti Kebangsaan Malaysia Medical Centre

This study aims to determine the prevalence of lower urinary tract symptoms (LUTS) and level of awareness among male outpatients in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). A questionnaire consisting of demographic data, questions related to knowledge, attitude and practice on BPH and the International Prostate Symptom Score (IPSS) was used for this study. Uroflowmetry and bladder scan were used to evaluate the function of the urinary tract and severity of BPH. Urine dipstick was done for glycosuria, proteinuria and haematuria. A total of 220 respondents were surveyed. The prevalence of moderately and severely symptomatic LUTS was 42.7%. The most commonly reported LUTS were nocturia (78.2%), frequency (58.2%) and incomplete emptying (44.6%). The prevalence of glycosuria, proteinuria and haematuria were 23.6%, 11.4% and 1.8% respectively. There was a significant association between increasing age with the severity of LUTS (p=0.005). Out of 102 respondents with voided urine volume greater than 150 mL, there was a significant decrease in maximum (Qmax) (p=0.039) and average (Qave) urine flow rates with every 10 years increase of age (p=0.001). The majority of respondents (59.5%) have heard of BPH before. Over 78.2% of the respondents would seek medical attention if they have LUTS with 15.9% saying they would seek traditional treatment. In conclusion, the prevalence of LUTS was high and the level of awareness was satisfactory.

Pentoxifylline as an adjunct therapy in children with cerebral malaria.

BACKGROUND: Pentoxifylline (PTX) affects many processes that may contribute to the pathogenesis of severe malaria and it has been shown to reduce the duration of coma in children with cerebral malaria. This pilot study was performed to assess pharmacokinetics, safety and efficacy of PTX in African children with cerebral malaria. METHODS: Ten children admitted to the high dependency unit of the Kilifi District Hospital in Kenya with cerebral malaria (Blantyre coma score of 2 or less) received quinine plus a continuous infusion of 10 mg/kg/24 hours PTX for 72 hours. Five children were recruited as controls and received normal saline instead of PTX. Plasma samples were taken for PTX and tumour necrosis factor (TNF) levels. Blantyre Coma Score, parasitemia, hematology and vital signs were assessed 4 hourly. RESULTS: One child (20%) in the control group died, compared to four children (40%) in the PTX group. This difference was not significant (p = 0.60). Laboratory parameters and clinical data were comparable between groups. TNF levels were lower in children receiving PTX. CONCLUSIONS: The small sample size does not permit definitive conclusions, but the mortality rate was unexpectedly high in the PTX group.

Clinicopathological features of bladder tumours in a single institution in Malaysia.

OBJECTIVE: To determine the clinicopathological features of bladder tumours encountered over a five year period in Universiti Kebangsaan Malaysia Medical Centre. METHODS: Medical records of bladder tumour cases from 2005 till 2009 were retrospectively reviewed and tabulated. RESULTS: A total of 83 cases were recorded. The incidence was highest among the Chinese (56.6%), followed by Malays (34.9%), Indians (6%) and other races (2.4%). The male-to-female ratio was 9.4:1. The median age was 65 years (range 30-91 years) and median duration of follow up was 17.2 months (range 2-60 months). The main histopathology was transitional cell carcinoma (TCC) (90.4%), followed by adenocarcinoma (6%), squamous cell carcinoma (1.2%), leiomyoma (1.2%) and myeloid sarcoma (1.2%). For the TCCs, 58.6% were superficial while 41.4% were muscle invasive, and 13.3% had nodal metastasis with distant metastasis in 8%. Of the total, 5.3% were papillary urothelial tumours of low malignant potential, 33.3% pTa, 20% pT1, 10.7% pT2, 12.0% pT3 and 18.7% pT4. Of the superficial tumours, 32.5% were high grade tumours. There were ten radical cystectomies performed for transitional cell carcinomas; two had neobladder reconstruction whereas the other eight had ileal conduits. All the adenocarcinomas and squamous cell carcinomas were treated by radiotherapy due to the advanced stage of the disease while the myeloid sarcoma received chemotherapy. Mean survival of patients with muscle invasive cancer was 33+/-5 months. By the end of the study, 18.1% of patients had died of their cancer. CONCLUSION: The incidence of bladder tumours is highest among the Chinese. When compared to other studies, the incidence of muscle invasive and high-grade superficial tumours was greater.

Spontaneous bladder perforation: a rare complication of tuberculosis.

Spontaneous bladder perforation secondary to tuberculosis (TB) is very rare. Only three cases have been reported so far in the literature. Due to its rarity, the diagnosis of spontaneous bladder perforation is often missed. Confirmation of TB via culture takes a long time and starting empirical treatment for TB is necessary. We relate our experience with a young woman who presented with clinical features of a perforated appendix and was only diagnosed with bladder perforation during laparotomy. She also had distal right ureteral stricture and left infundibular stenosis. The provisional diagnosis of TB was attained via typical histopathological features and a positive Mantoux test. She was started empirically on anti-TB treatment and recovered without any complications. Urine culture after 6 weeks confirmed the diagnosis of TB.

Seven-year review of prostate carcinomas diagnosed by TRUS biopsy in a single Malaysian institution.

INTRODUCTION: Analysis of epidemiological as well as survival differences among the multiethnic population of Malaysia with prostate cancer is important. METHODS: Patients confirmed by transrectal-ultrasonographic-guided-biopsy performed from 2002 to 2008 were enrolled and analysed according to ethnicity, age, PSA level, Gleason score, stage of disease and survival. RESULTS: Among 83 patients, there were 38 Malay, 40 Chinese, 3 Indians and 2 others. Median age at diagnosis was 69.9 (range: 59-93), 43 patients (51.8%) being diagnosed before the age of 70. The median PSA level upon diagnosis was 574 ng/ml (range: 1-8632) and the median Gleason score was 7 (range: 2-10). Over half were already in Stage 4 when diagnosed. The most common site of metastasis was the bone. As a result the commonest prescribed treatment was hormonal manipulation. Five patients underwent radical prostatectomy and a further thirteen patients had radical radiotherapy (stage I: 1 patient, stage II: 7 patients and stage III: 5 patients). Ten patients defaulted follow-up. The median disease-specific survival was 21.9 months (range: 1-53). CONCLUSIONS: Prostatic carcinoma is a disease of the elderly and it is frequently diagnosed late in Malaysia. Greater efforts should be made to educate Malaysians regarding prostate cancer.

A prospective, randomized clinical trial comparing bipolar plasma kinetic resection of the prostate versus conventional monopolar transurethral resection of the prostate in the treatment of benign prostatic hyperplasia.

BACKGROUND AND OBJECTIVE: For treatment of benign prostatic hyperplasia (BPH), Plasma Kinetic loop Resection of the Prostate (PKRP) is an alternative to conventional monopolar transurethral resection of prostate (TURP). We compared outcomes with the two treatments in a randomized trial. PATIENTS AND METHODS: Over a one-year period, we randomly assigned patients with an indication for surgery for BPH and who met inclusion criteria to treatment with either PKRP or TURP. We measured prostate volume by transrectal ultrasound, relief of bladder outlet obstruction, operative time, decline in serum sodium and hemoglobin, weight of resected prostatic chips, duration of catheterization and hospital stay. Patients were evaluated one month after discharge for obstructive symptoms. Complications were also recorded. RESULTS: Of 102 patients enrolled, 51 underwent PKRP and 51 underwent TURP. Relief of obstructive symptoms and mean operative time showed no statistically significant difference. The PKRP group had a smaller decline in hemoglobin than the TURP group (0.6 g/dL vs 1.8 g/dL, P=.01), a lower reduction in serum sodium levels (1.03 mmol/L vs 5.01 mmol/L, P=.01), a shorter catheterization time (37.2 hours versus 57.7 hours, P=.03) and a shorter hospital stay (1.5 days versus 2.6 days, P=.02). One patient in the bipolar PKRP group needed recatheterization versus four patients in the TURP group. CONCLUSION: PKRP reduces morbidity with an outcome similar to conventional monopolar TURP in the treatment of BPH.