Efficacy, Safety and Tolerability of Valsartan and Hydrochlorothiazide Compared to Valsartan and Amlodipine in Stage 2 Hypertension

Background: Hypertension is a growing medical and public health issue. The United States and European treatment guidelines have been issued to attain smooth control of hypertension in various categories of patients. It is a need of time to unveil safe combination therapies in various populations. Objectives: (i) To determine the efficacy of valsartan and hydrochlorothiazide versus valsartan and amlodipine (ii) To determine the safety and tolerability of both combinations. Materials & Methods: This experimental study was conducted at Shalamar Hospital Lahore. 126 patients with stage 2 hypertension were recruited from the medical outdoor of Shalamar Hospital Lahore after getting informed consent. In group A, 63 patients were given valsartan and hydrochlorothiazide. In group B, 63 patients were given valsartan and amlodipine. Blood pressure (BP) of both study groups was recorded on day zero, 2nd, 4th, and 8th weeks and the readings were entered on a Proforma. The efficacy of drug combinations was accessed in both groups by recording the change in mean systolic blood pressure (MSBP) and mean diastolic blood pressure (MDBP). The safety and tolerability of the drug combinations were assessed in terms of side effects and laboratory findings. Results: In group A, there was a 39±7mmzHg and 18±1mmHg decrease in MSBP and MDBP, respectively, from baseline BP. In group B, there was a 26.7±4mmHg and 14±2 mmHg decrease in MSBP and MDBP, respectively, from baseline BP. Both combinations were safe, and no significant difference in the efficacy of both combinations was observed after 8-week of treatment. Conclusion: Both combinations are effective for control of BP, but the valsartan and hydrochlorothiazide combination (group A) appears to have better tolerability and greater effect in decreasing BP as compared to the combination of valsartan and amlodipine (group B), although this difference is not statistically significant.  

Hydrological Response of Snow Covered Glaciated Catchments to Energy Balance and Temperature Index Methods

The importance of reservoirs, lakes and dams for drinking water supply, irrigation, flood control and electricity generation is widely acknowledged across the globe. In Pakistan, half of the electricity production is made through hydropower plants and dams. Pakistan is highly dependent on water generated, from the snow and ice melting in the mountainous regions of Karakoram. The water available in these catchments comes mainly from snow and glaciers melt. However, these watersheds are highly sensitive to climate change. Pakistan is one of the high risk countries considering the adverse effects of global warming due to its particular geography and climate. Variation of temperature and precipitation trends already resulted in alternative droughts and floods at various places. Consequently, the quantification of these changes at the right time is an important challenge for water resources managers. This study presents the comparison of two different models commonly used to simulate snow and ice melt in the high altitude snow covered mountainous watersheds. Two types of methods are commonly used to quantify the melting i.e. physics-based energy-balance model and the conceptual Positive Degree-Day Index (PDDI) model. The energy-balance based model calculated all the available energy fluxes to quantify melt. On the other hand temperature index based models consider melt as function of air temperature. The objective of this study is to analyze the differences of these models and assess their ability to simulate runoff in high altitude catchment with glacio-nival runoff regimes. This detail report details the comparison of these two melt methods in three high altitude catchments. A unique approach is implemented by using one numerical model framework to run both the melt schemes i.e EB and TI. Alpine3D has been modified to run TI melt scheme to let on investigate the associated uncertainties of each modeling approach. This approach will be expected to eliminate various uncertainty sources including errors that may come from the use of variety of interpolation schemes augmented in different tools. For better comparison and analysis, the model system was driven on three high-altitude glaciated basins. Two out of three study basins (Damma and Arolla) are located in Switzerland whereas; third basin (Passu) is located in Pakistan. These catchments represent different kinds of glaciers and have been selected due to their catchment area, input data coverage and other hydro-meteorological and climatic data availability. The quick convergence of the degree-day model to reasonable results is observed, even if its limits are discussed. On the other hand, the high sensitivity of the energy-balance model to input datasets is noticed, particularly to wind speed which leads to melt overestimation in Damma catchment. Moreover, the air temperature overestimation due to the presence of katabatic winds on the Damma glacier is found to explain the remaining melt overestimation revealed by this model. Consequently, improvements are suggested to obtain more robust results with the energy-balance model. As a first step, wind speed is corrected by using new weather stations located at high altitude. Whereas, EB melt model demonstrated high performance at Arolla Catchment. This is because; highly representative meteorological data set was used from local weather stations located near the catchment boundary. In addition model was driven with the available temperature data measured at a 2 meter height and better represents the glacier surface conditions. On the other hand, both the model types failed represent the correct melt and discharge dynamics at Passu glacier mainly due to the non-availability of quality data sets. This shortcoming limited the thorough comparison of the models at this place. However this report highlight the importance and improvements needed and provides a firm base for energy balance modeling and this kind of comparison in Pakistan. Relative difference between the Energy Balance and Temperature Index simulations by a distributed energy balance model was very small despite the use of a simplified basic TI melt scheme without on-site calibration. This reveals that the use a highly accurate energy balance model SNOWPACK and Alpine3D have diminished various sources uncertainties. This report concludes that testing two melt schemes in a single model plays a very important role towards understanding melt dynamics and catchment hydrology. Special attention must be given to model calibration procedure for such kind of comparison. Quality input data sets and a long term measurement record plays a vital role in accuracy. EB balance based melt models are highly sensitive to the meteorological input variables and their correct spatial representation, which is extremely hard to achieve especially in rugged high altitude glacier rich terrains.